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

Author

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

Published
2024
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2. Bloch waves and Non-commutative Tori of Magnetic Translations

Author

Dereli, Tekin and Popov, Todor

Subjects
Mathematical Physics, Condensed Matter - Strongly Correlated Electrons
Abstract

We review the Landau problem of an electron in a constant uniform magnetic field. The magnetic translations are the invariant transformations of the free Hamiltonian. A K\"ahler polarization of the plane has been used for the geometric quantization. Under the assumption of quasi-periodicity of the wavefunction the magnetic translations in the Bravais lattice generate a non-commutative quantum torus. We concentrate on the case when the magnetic flux density is a rational number. The Bloch wavefunctions form a finite-dimensional module of the noncommutative torus of magnetic translations as well as of its commutant which is the non-commutative torus of magnetic translation in the dual Bravais lattice. The bi-module structure of the Bloch waves is shown to be the connecting link between two Morita equivalent non-commutative tori., Comment: 23 pages

Published
2021
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3. Quantum Diagonal Algebra and Pseudo-Plactic Algebra

Author

Popov, Todor

Subjects
Mathematics - Quantum Algebra
Abstract

The subalgebra of diagonal elements of a quantum matrix group has been conjectured by Daniel Krob and Jean-Yves Thibon to be isomorphic to a cubic algebra, coined the quantum pseudo-plactic algebra. We present a functorial approach to the conjecture through the quantum Schur-Weyl duality between the quantum group and the Hecke algebra. The relations of the quantum diagonal subalgebra are found to be the image of the braid relations of the underlying Hecke algebra by an appropriate Schur functor which gives a straightforward proof of the conjecture., Comment: 14 pages, talk given at XIII-th International Workshop Lie Theory and Its Applications in Physics" (Varna,Bulgaria, June 2019)

Published
2019

4. Pre-Plactic Algebra and Snakes

Author

Popov, Todor

Subjects
Mathematics - Quantum Algebra
Abstract

We study a factor Hopf algebra $\mathfrak{PP}$ of the Malvenuto-Reutenauer convolution algebra of functions on symmetric groups ${\mathfrak{S}}=\oplus_{n\geq 0} \mathbb C[{\mathfrak{S}}_n] $ that we coined pre-plactic algebra. The pre-plactic algebra admits the Poirier-Reutenauer algebra based on Standard Young Tableaux as a factor and it is closely related to the quantum pseudo-plactic algebra introduced by Krob and Thibon in the non-commutative character theory of quantum group comodules. The connection between the quantum pseudo-plactic algebra and the pre-plactic algebra is similar to the connection between the Lascoux-Sch\"utzenberger plactic algebra and the Poirier-Reutenauer algebra. We show that the dimensions of the pre-plactic algebra are given by the numbers of alternating permutations (coined snakes after V.I. Arnold). Pre-plactic algebra is instrumental in calculating the Hilbert-Poincar\'e series of the quantum pseudo-plactic algebra., Comment: 12 pages. Comments are welcome!

Published
2017

5. A Critical Review on microRNAs as Prognostic Biomarkers in Laryngeal Carcinoma.

Author

Komitova, Kristina S., Dimitrov, Lyuben D., Stancheva, Gergana S., Kyurkchiyan, Silva G., Petkova, Veronika, Dimitrov, Stoyan I., Skelina, Silviya P., Kaneva, Radka P., and Popov, Todor M.

Abstract

During the past decade, a vast number of studies were dedicated to unravelling the obscurities of non-coding RNAs in all fields of the medical sciences. A great amount of data has been accumulated, and consequently a natural need for organization and classification in all subfields arises. The aim of this review is to summarize all reports on microRNAs that were delineated as prognostic biomarkers in laryngeal carcinoma. Additionally, we attempt to allocate and organize these molecules according to their association with key pathways and oncogenes affected in laryngeal carcinoma. Finally, we critically analyze the common shortcomings and biases of the methodologies in some of the published papers in this area of research. A literature search was performed using the PubMed and MEDLINE databases with the keywords "laryngeal carcinoma" OR "laryngeal cancer" AND "microRNA" OR "miRNA" AND "prognostic marker" OR "prognosis". Only research articles written in English were included, without any specific restrictions on study type. We have found 43 articles that report 39 microRNAs with prognostic value associated with laryngeal carcinoma, and all of them are summarized along with the major characteristics and methodology of the respective studies. A second layer of the review is structural analysis of the outlined microRNAs and their association with oncogenes and pathways connected with the cell cycle (p53, CCND1, CDKN2A/p16, E2F1), RTK/RAS/PI3K cascades (EGFR, PI3K, PTEN), cell differentiation (NOTCH, p63, FAT1), and cell death (FADD, TRAF3). Finally, we critically review common shortcomings in the methodology of the papers and their possible effect on their results. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Medical devices in allergy practice

Author

Popov, Todor A., Passalacqua, Gianni, González-Díaz, Sandra N., Plavec, Davor, Braido, Fulvio, García-Abujeta, Jose-Luis, Dubuske, Lawrence, Rouadi, Philip, Morais-Almeida, Mário, Bonini, Sergio, Cheng, Lei, and Ansotegui, Ignacio J.

Published
2020
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9. International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies

Author

Naclerio, Robert, Ansotegui, Ignacio J., Bousquet, Jean, Canonica, G. Walter, D'Amato, Gennaro, Rosario, Nelson, Pawankar, Ruby, Peden, David, Bergmann, Karl-Christian, Bielory, Leonard, Caraballo, Luis, Cecchi, Lorenzo, Cepeda, S. Alfonso M., Chong Neto, Herberto José, Galán, Carmen, Gonzalez Diaz, Sandra N., Idriss, Samar, Popov, Todor, Ramon, German D., Ridolo, Erminia, Rottem, Menachem, Songnuan, Wisuwat, and Rouadi, Philip

Published
2020
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10. Parafermionic algebras, their modules and cohomologies

Author

Popov, Todor

Subjects
Mathematical Physics, 17B56, 17B01, 13D02
Abstract

We explore the Fock spaces of the parafermionic algebra introduced by H.S. Green. Each parafermionic Fock space allows for a free minimal resolution by graded modules of the graded 2-step nilpotent subalgebra of the parafermionic creation operators. Such a free resolution is constructed with the help of a classical Kostant's theorem computing Lie algebra cohomologies of the nilpotent subalgebra with values in the parafermionic Fock space. The Euler-Poincar\'e characteristics of the parafermionic Fock space free resolution yields some interesting identities between Schur polynomials. Finally we briefly comment on parabosonic and general parastatistics Fock spaces., Comment: 10 pages, talk presented at the International Workshop "Lie theory and its applications in Physics" (17-23 June 2013, Varna, Bulgaria)

Published
2014

11. Real-world biologics response and super-response in the International Severe Asthma Registry cohort

Author

Denton, Eve, Hew, Mark, Peters, Matthew J., Upham, John W., Bulathsinhala, Lakmini, Tran, Trung N., Martin, Neil, Bergeron, Celine, Al-Ahmad, Mona, Altraja, Alan, Larenas-Linnemann, Desiree, Murray, Ruth, Celis-Preciado, Carlos Andres, Al-Lehebi, Riyad, Belhassen, Manon, Bhutani, Mohit, Bosnic-Anticevich, Sinthia Z., Bourdin, Arnaud, Brusselle, Guy G., Busby, John, Canonica, Giorgio Walter, Heffler, Enrico, Chapman, Kenneth R., Charriot, Jeremy, Christoff, George C., Chung, Li Ping, Cosio, Borja G., Cote, Andreanne, Costello, Richard W., Cushen, Breda, Fingleton, James, Fonseca, Joao A., Gibson, Peter G., Heaney, Liam G., Huang, Erick Wan-Chun, Iwanaga, Takashi, Jackson, David J., Koh, Mariko Siyue, Lehtimaki, Lauri, Maspero, Jorge, Mahboub, Bassam, Menzies-Gow, Andrew N., Mitchell, Patrick D., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng, Diahn-Warng, Pfeffer, Paul E., Popov, Todor A., Porsbjerg, Celeste M., Denton, Eve, Hew, Mark, Peters, Matthew J., Upham, John W., Bulathsinhala, Lakmini, Tran, Trung N., Martin, Neil, Bergeron, Celine, Al-Ahmad, Mona, Altraja, Alan, Larenas-Linnemann, Desiree, Murray, Ruth, Celis-Preciado, Carlos Andres, Al-Lehebi, Riyad, Belhassen, Manon, Bhutani, Mohit, Bosnic-Anticevich, Sinthia Z., Bourdin, Arnaud, Brusselle, Guy G., Busby, John, Canonica, Giorgio Walter, Heffler, Enrico, Chapman, Kenneth R., Charriot, Jeremy, Christoff, George C., Chung, Li Ping, Cosio, Borja G., Cote, Andreanne, Costello, Richard W., Cushen, Breda, Fingleton, James, Fonseca, Joao A., Gibson, Peter G., Heaney, Liam G., Huang, Erick Wan-Chun, Iwanaga, Takashi, Jackson, David J., Koh, Mariko Siyue, Lehtimaki, Lauri, Maspero, Jorge, Mahboub, Bassam, Menzies-Gow, Andrew N., Mitchell, Patrick D., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng, Diahn-Warng, Pfeffer, Paul E., Popov, Todor A., and Porsbjerg, Celeste M.

Abstract

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV 1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV 1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV 1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40–50% of initiators did not meet response criteria. Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40–50% did not meet the response criteria.

Published
2024

12. Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma

Author

Porsbjerg, Celeste M., Townend, John, Bergeron, Celine, Christoff, George C., Katsoulotos, Gregory P., Larenas-Linnemann, Desiree, Tran, Trung N., Al-Lehebi, Riyad, Bosnic-Anticevich, Sinthia Z., Busby, John, Hew, Mark, Kostikas, Konstantinos, Papadopoulos, Nikolaos G., Pfeffer, Paul E., Popov, Todor A., Rhee, Chin Kook, Sadatsafavi, Mohsen, Tsai, Ming-Ju, Ulrik, Charlotte Suppli, Al-Ahmad, Mona, Altraja, Alan, Beastall, Aaron, Bulathsinhala, Lakmini, Carter, Victoria, Cosio, Borja G., Fletton, Kirsty, Hansen, Susanne, Heaney, Liam G., Hubbard, Richard B., Kuna, Piotr, Murray, Ruth B., Nagano, Tatsuya, Pini, Laura, Rosales, Diana Jimena Cano, Schleich, Florence, Wechsler, Michael E., Amaral, Rita, Bourdin, Arnaud, Brusselle, Guy G., Chen, Wenjia, Chung, Li Ping, Denton, Eve, Fonseca, Joao A., Hoyte, Flavia, Jackson, David J., Katial, Rohit, Kirenga, Bruce J., Koh, Mariko Siyue, Lawkiedraj, Agnieszka, Lehtimaki, Lauri, Liew, Mei Fong, Mahboub, Bassam, Martin, Neil, Menzies-Gow, Andrew N., Pang, Pee Hwee, Papaioannou, Andriana I., Patel, Pujan H., Perez-De-Llano, Luis, Peters, Matthew J., Ricciardi, Luisa, Rodriguez-Caceres, Bellanid, Solarte, Ivan, Tay, Tunn Ren, Torres-Duque, Carlos A., Wang, Eileen, Zappa, Martina, Abisheganaden, John, Assing, Karin Dahl, Costello, Richard W., Gibson, Peter G., Heffler, Enrico, Maspero, Jorge, Nicola, Stefania, Steve, Diahn-Warng Perng, Puggioni, Francesca, Salvi, Sundeep, Sheu, Chau-Chyun, Sirena, Concetta, Taille, Camille, Tan, Tze Lee, Bjermer, Leif, Canonica, Giorgio Walter, Iwanaga, Takashi, Jimenez-Maldonado, Libardo, Taube, Christian, Brussino, Luisa, Price, David B., Porsbjerg, Celeste M., Townend, John, Bergeron, Celine, Christoff, George C., Katsoulotos, Gregory P., Larenas-Linnemann, Desiree, Tran, Trung N., Al-Lehebi, Riyad, Bosnic-Anticevich, Sinthia Z., Busby, John, Hew, Mark, Kostikas, Konstantinos, Papadopoulos, Nikolaos G., Pfeffer, Paul E., Popov, Todor A., Rhee, Chin Kook, Sadatsafavi, Mohsen, Tsai, Ming-Ju, Ulrik, Charlotte Suppli, Al-Ahmad, Mona, Altraja, Alan, Beastall, Aaron, Bulathsinhala, Lakmini, Carter, Victoria, Cosio, Borja G., Fletton, Kirsty, Hansen, Susanne, Heaney, Liam G., Hubbard, Richard B., Kuna, Piotr, Murray, Ruth B., Nagano, Tatsuya, Pini, Laura, Rosales, Diana Jimena Cano, Schleich, Florence, Wechsler, Michael E., Amaral, Rita, Bourdin, Arnaud, Brusselle, Guy G., Chen, Wenjia, Chung, Li Ping, Denton, Eve, Fonseca, Joao A., Hoyte, Flavia, Jackson, David J., Katial, Rohit, Kirenga, Bruce J., Koh, Mariko Siyue, Lawkiedraj, Agnieszka, Lehtimaki, Lauri, Liew, Mei Fong, Mahboub, Bassam, Martin, Neil, Menzies-Gow, Andrew N., Pang, Pee Hwee, Papaioannou, Andriana I., Patel, Pujan H., Perez-De-Llano, Luis, Peters, Matthew J., Ricciardi, Luisa, Rodriguez-Caceres, Bellanid, Solarte, Ivan, Tay, Tunn Ren, Torres-Duque, Carlos A., Wang, Eileen, Zappa, Martina, Abisheganaden, John, Assing, Karin Dahl, Costello, Richard W., Gibson, Peter G., Heffler, Enrico, Maspero, Jorge, Nicola, Stefania, Steve, Diahn-Warng Perng, Puggioni, Francesca, Salvi, Sundeep, Sheu, Chau-Chyun, Sirena, Concetta, Taille, Camille, Tan, Tze Lee, Bjermer, Leif, Canonica, Giorgio Walter, Iwanaga, Takashi, Jimenez-Maldonado, Libardo, Taube, Christian, Brussino, Luisa, and Price, David B.

Abstract

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for antiI-IL4R alpha. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/mu L), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and - anti- IL4R alpha, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4R alpha, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for

Published
2024
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13. Drinfeld-Jimbo quantum Lie algebra

Author

Ogievetsky, Oleg and Popov, Todor

Subjects
Mathematics - Quantum Algebra
Abstract

Quantum Lie algebras related to multi-parametric Drinfeld-Jimbo $R$-matrices of type $GL(m|n)$ are classified., Comment: 9 pages

Published
2012
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14. Young tableaux and homotopy commutative algebras

Author

Dubois-Violette, Michel and Popov, Todor

Subjects
Mathematics - Quantum Algebra, Mathematical Physics, Mathematics - Rings and Algebras
Abstract

A homotopy commutative algebra, or $C_{\infty}$-algebra, is defined via the Tornike Kadeishvili homotopy transfer theorem on the vector space generated by the set of Young tableaux with self-conjugated Young diagrams. We prove that this $C_{\infty}$-algebra is generated in degree 1 by the binary and the ternary operations., Comment: Talk given by Todor Popov at the International Workshop "Lie Theory-IX", Varna, 2011, (11 pages)

Published
2012

15. Parastatistics Algebra, Young Tableaux and the Super Plactic Monoid

Author

Loday, Jean-Louis and Popov, Todor

Subjects
Mathematical Physics, Mathematics - Quantum Algebra
Abstract

The parastatistics algebra is a superalgebra with (even) parafermi and (odd) parabose creation and annihilation operators. The states in the parastatistics Fock-like space are shown to be in one-to-one correspondence with the Super Semistandard Young Tableaux (SSYT) subject to further constraints. The deformation of the parastatistics algebra gives rise to a monoidal structure on the SSYT which is a super-counterpart of the plactic monoid., Comment: Presented at the International Workshop "Differential Geometry, Noncommutative Geometry, Homology and Fundamental Interactions" in honour of Michel Dubois-Violette, Orsay, April 8-10, 2008

Published
2008
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16. On rime Ansatz

Author

Ogievetsky, Oleg and Popov, Todor

Subjects
Mathematics - Quantum Algebra
Abstract

The ice Ansatz on matrix solutions of the Yang-Baxter equation is weakened to a condition which we call rime. Generic rime solutions of the Yang-Baxter equation are described. We prove that the rime non-unitary (respectively, unitary) R-matrix is equivalent to the Cremmer-Gervais (respectively, boundary Cremmer-Gervais) solution. Generic rime classical r-matices satisfy the (non-)homogeneous associative classical Yang-Baxter equation., Comment: 4 pages, talk given at the VII International Workshop "Supersymmetries and Quantum Symmetries", Dubna 2007

Published
2007

17. Parastatistics Algebra and Super Semistandard Young Tableaux

Author

Loday, Jean-Louis and Popov, Todor

Subjects
Mathematical Physics
Abstract

We consider the parastatistics algebra with both parabosonic and parafermionic operators and show that the states in the universal parastatistics Fock space are in bijection with the Super Semistandard Young Tableaux (SSYT). Using deformation of the parastatistics algebra we get a monoid structure on SSYT which is a super version of the plactic monoid., Comment: 8 pages, based on a talk given at the VII International Workshop "Lie Theory and Its Applications in Physics" Varna, 18-24 June 2007

Published
2007

18. Automorphisms of Regular Algebras

Author

Popov, Todor

Subjects
Mathematics - Quantum Algebra
Abstract

Manin associated to a quadratic algebra (quantum space) the quantum matrix group of its automorphisms. This Talk aims to demonstrate that Manin's construction can be extended for quantum spaces which are non-quadratic homogeneous algebras. Here given a regular Artin-Schelter algebra of dimension 3 we construct the quantum group of its symmetries, i.e., the Hopf algebra of its automorphisms. For quadratic Artin-Schelter algebras these quantum groups are contained in the the classification of the GL(3) quantum matrix groups due to Ewen and Ogievetsky. For cubic Artin-Schelter algebras we obtain new quantum groups which are automorphisms of cubic quantum spaces., Comment: 8 pages, based on a talk at the International Workshop "Lie Theory and Its Applications in Physics VI" Varna, 2005

Published
2006

19. Hopf Structure and Green Ansatz of Deformed Parastatistics Algebras

Author

Aneva, Boyka and Popov, Todor

Subjects
Mathematical Physics, Mathematics - Quantum Algebra
Abstract

Deformed parabose and parafermi algebras are revised and endowed with Hopf structure in a natural way. The noncocommutative coproduct allows for construction of parastatistics Fock-like representations, built out of the simplest deformed bose and fermi representations. The construction gives rise to quadratic algebras of deformed anomalous commutation relations which define the generalized Green ansatz., Comment: 14 pages, final version

Published
2004
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20. Homogeneous algebras, statistics and combinatorics

Author

Dubois-Violette, Michel and Popov, Todor

Subjects
Mathematics - Quantum Algebra, High Energy Physics - Theory, Mathematical Physics
Abstract

After some generalities on homogeneous algebras, we give a formula connecting the Poincar\'e series of a homogeneous algebra with the homology of the corresponding Koszul complex generalizing thereby a standard result for quadratic algebras. We then investigate two particular types of cubic algebras: The first one called the parafermionic (parabosonic) algebra is the algebra generated by the creation operators of the universal fermionic (bosonic) parastatics with $D$ degrees of freedom while the second is the plactic algebra that is the algebra of the plactic monoid with entries in $\{1,2,..., D\}$. In the case D=2 we describe the relations with the cubic Artin-Schelter algebras. It is pointed out that the natural action of GL(2) on the parafermionic algebra for D=2 extends as an action of the quantum group $GL_{p,q}(2)$ on the generic cubic Artin-Schelter regular algebra of type $S_1$; $p$ and $q$ being related to the Artin-Schelter parameters. It is claimed that this has a counterpart for any integer $D\geq 2$., Comment: 14 pages

Published
2002

21. On the rational solutions of the su(2)_k Knizhnik-Zamolodchikov equation

Author

Hadjiivanov, Ludmil and Popov, Todor

Subjects
High Energy Physics - Theory, Mathematical Physics, Mathematics - Quantum Algebra, Nonlinear Sciences - Exactly Solvable and Integrable Systems
Abstract

We present some new results on the rational solutions of the Knizhnik-Zamolodchikov equation for the four-point conformal blocks of isospin I primary fields in the SU(2)_k Wess-Zumino-Novikov-Witten model. The rational solutions corresponding to integrable representations of the affine algebra su(2)_k have been classified by Michel, Stanev and Todorov; provided that the conformal dimension is an integer, they are in one-to-one correspondence with the local extensions of the chiral algebra. Here we give another description of these solutions as specific braid-invariant combinations of the so called regular basis and display a new series of rational solutions for isospins I = k+1 corresponding to non-integrable representations of the affine algebra., Comment: EPJ LaTeX Style, amsfonts, 4 pages. A couple of small corrections inserted. Submitted for publication in the Proceedings of the Conference on Geometry, Integrability and Nonlinearity in Condensed Matter and Soft Condensed Matter Physics, 15-20 July 2001, Bansko (Bulgaria)

Published
2001
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22. International severe asthma registry (ISAR): protocol for a global registry

Author

FitzGerald, J. Mark, Tran, Trung N., Alacqua, Marianna, Altraja, Alan, Backer, Vibeke, Bjermer, Leif, Bjornsdottir, Unnur, Bourdin, Arnaud, Brusselle, Guy, Bulathsinhala, Lakmini, Busby, John, Canonica, Giorgio W., Carter, Victoria, Chaudhry, Isha, Cho, You Sook, Christoff, George, Cosio, Borja G., Costello, Richard W., Eleangovan, Neva, Gibson, Peter G., Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hosseini, Naeimeh, Iwanaga, Takashi, Jackson, David J., Jones, Rupert, Koh, Mariko S., Le, Thao, Lehtimäki, Lauri, Ludviksdottir, Dora, Maitland-van der Zee, Anke H., Menzies-Gow, Andrew, Murray, Ruth B., Papadopoulos, Nikolaos G., Perez-de-Llano, Luis, Peters, Matthew, Pfeffer, Paul E., Popov, Todor A., Porsbjerg, Celeste M., Price, Chris A., Rhee, Chin K., Sadatsafavi, Mohsen, Tohda, Yuji, Wang, Eileen, Wechsler, Michael E., Zangrilli, James, and Price, David B.

Published
2020
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23. Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

Author

Kyurkchiyan, Silva G., Stancheva, Gergana, Petkova, Veronika, Panova, Stiliana, Dobriyanova, Venera, Stancheva, Iglika, Marinov, Venelin, Zahariev, Zahari, Kaneva, Radka P., and Popov, Todor M.

Subjects
MUCOUS membranes, CARCINOMA, TUMORS, TISSUES, TREATMENT effectiveness
Abstract

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer—the process of tumor neoangiogenesis. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Landau Levels versus Hydrogen Atom.

Author

Dereli, Tekin, Nounahon, Philippe, and Popov, Todor

Subjects
LANDAU levels, HARMONIC oscillators, HILBERT space, ANGULAR momentum (Mechanics), KEPLER problem, SYMMETRY breaking, HYDROGEN atom
Abstract

The Landau problem and harmonic oscillator in the plane share a Hilbert space that carries the structure of Dirac's remarkable s o (2 , 3) representation. We show that the orthosymplectic algebra o s p (1 | 4) is the spectrum generating algebra for the Landau problem and, hence, for the 2D isotropic harmonic oscillator. The 2D harmonic oscillator is in duality with the 2D quantum Coulomb–Kepler systems, with the o s p (1 | 4) symmetry broken down to the conformal symmetry s o (2 , 3) . The even s o (2 , 3) submodule (coined Rac) generated from the ground state of zero angular momentum is identified with the Hilbert space of a 2D hydrogen atom. An odd element of the superalgebra o s p (1 | 4) creates a pseudo-vacuum with intrinsic angular momentum 1/2 from the vacuum. The odd s o (2 , 3) -submodule (coined Di) built upon the pseudo-vacuum is the Hilbert space of a magnetized 2D hydrogen atom: a quantum system of a dyon and an electron. Thus, the Hilbert space of the Landau problem is a direct sum of two massless unitary s o (2 , 3) representations, namely, the Di and Rac singletons introduced by Flato and Fronsdal. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Impact of Inititing Biologics in Patients With Severe Asthma on Long-term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER):Data From the International Severe Asthma Registry

Author

Chen, Wenjia, Tran, Trung N., Sadatsafavi, Mohsen, Murray, Ruth, Wong, Nigel Chong Boon, Ali, Nasloon, Ariti, Con, Bulathsinhala, Lakmini, Gil, Esther Garcia, FitzGerald, J. Mark, Alacqua, Marianna, Al-Ahmad, Mona, Altraja, Alan, Al-Lehebi, Riyad, Bhutani, Mohit, Bjermer, Leif, Bjerrum, Anne Sofie, Bourdin, Arnaud, von Bülow, Anna, Busby, John, Canonica, Giorgio Walter, Carter, Victoria, Christoff, George C., Cosio, Borja G., Costello, Richard W., Fonseca, João A., Gibson, Peter G., Yoo, Kwang Ha, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Iwanaga, Takashi, Jackson, David J., Jones, Rupert C., Koh, Mariko Siyue, Kuna, Piotr, Larenas-Linnemann, Désirée, Lehmann, Sverre, Lehtimäki, Lauri, Lyu, Juntao, Mahboub, Bassam, Maspero, Jorge, Menzies-Gow, Andrew N., Newell, Anthony, Sirena, Concetta, Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng (Steve), Diahn Warng, Peters, Matthew, Pfeffer, Paul E., Porsbjerg, Celeste M., Popov, Todor A., Rhee, Chin Kook, Salvi, Sundeep, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Ra, Seung Won, Wang, Eileen, Wechsler, Michael E., Price, David B., Chen, Wenjia, Tran, Trung N., Sadatsafavi, Mohsen, Murray, Ruth, Wong, Nigel Chong Boon, Ali, Nasloon, Ariti, Con, Bulathsinhala, Lakmini, Gil, Esther Garcia, FitzGerald, J. Mark, Alacqua, Marianna, Al-Ahmad, Mona, Altraja, Alan, Al-Lehebi, Riyad, Bhutani, Mohit, Bjermer, Leif, Bjerrum, Anne Sofie, Bourdin, Arnaud, von Bülow, Anna, Busby, John, Canonica, Giorgio Walter, Carter, Victoria, Christoff, George C., Cosio, Borja G., Costello, Richard W., Fonseca, João A., Gibson, Peter G., Yoo, Kwang Ha, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Iwanaga, Takashi, Jackson, David J., Jones, Rupert C., Koh, Mariko Siyue, Kuna, Piotr, Larenas-Linnemann, Désirée, Lehmann, Sverre, Lehtimäki, Lauri, Lyu, Juntao, Mahboub, Bassam, Maspero, Jorge, Menzies-Gow, Andrew N., Newell, Anthony, Sirena, Concetta, Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Perez-de-Llano, Luis, Perng (Steve), Diahn Warng, Peters, Matthew, Pfeffer, Paul E., Porsbjerg, Celeste M., Popov, Todor A., Rhee, Chin Kook, Salvi, Sundeep, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Ra, Seung Won, Wang, Eileen, Wechsler, Michael E., and Price, David B.

Abstract

Background Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. Objective To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. Methods This was a propensity score–matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. Results We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). Conclusions In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization., Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. Methods: This was a propensity score–matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. Results: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). Conclusions: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Published
2023

27. Comparative effectiveness of anti-IL5 and anti-IgE biologic classes in patients with severe asthma eligible for both

Author

Pfeffer, Paul E., Ali, Nasloon, Murray, Ruth, Ulrik, Charlotte, Tran, Trung N., Maspero, Jorge, Peters, Matthew, Christoff, George C., Sadatsafavi, Mohsen, Torres-Duque, Carlos A., Altraja, Alan, Lehtimäki, Lauri, Papadopoulos, Nikolaos G, Salvi, Sundeep, Costello, Richard W., Cushen, Breda, Heffler, Enrico, Iwanaga, Takashi, Al-Ahmad, Mona, Larenas-Linnemann, Désirée, Kuna, Piotr, Fonseca, João A., Al-Lehebi, Riyad, Rhee, Chin Kook, Perez-de-Llano, Luis, Perng Steve, Diahn Warng, Mahboub, Bassam, Wang, Eileen, Goh, Celine, Lyu, Juntao, Newell, Anthony, Alacqua, Marianna, Belevskiy, Andrey S., Bhutani, Mohit, Bjermer, Leif, Bjornsdottir, Unnur, Bourdin, Arnaud, Bulow, Anna von, Busby, John, Canonica, Giorgio Walter, Cosio, Borja G., Dorscheid, Delbert R., Muñoz-Esquerre, Mariana, FitzGerald, J. Mark, Gil, Esther Garcia, Gibson, Peter G., Heaney, Liam G., Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Jackson, David J., Koh, Mariko Siyue, Ko, Hsin Kuo Bruce, Lee, Jae Ha, Lehmann, Sverre, Chaves Loureiro, Cláudia, Lúðvíksdóttir, Dóra, Menzies-Gow, Andrew N., Mitchell, Patrick, Papaioannou, Andriana I., Popov, Todor A., Porsbjerg, Celeste M., Salameh, Laila, Sirena, Concetta, Taillé, Camille, Taube, Christian, Tohda, Yuji, Wechsler, Michael E., Price, David B., Pfeffer, Paul E., Ali, Nasloon, Murray, Ruth, Ulrik, Charlotte, Tran, Trung N., Maspero, Jorge, Peters, Matthew, Christoff, George C., Sadatsafavi, Mohsen, Torres-Duque, Carlos A., Altraja, Alan, Lehtimäki, Lauri, Papadopoulos, Nikolaos G, Salvi, Sundeep, Costello, Richard W., Cushen, Breda, Heffler, Enrico, Iwanaga, Takashi, Al-Ahmad, Mona, Larenas-Linnemann, Désirée, Kuna, Piotr, Fonseca, João A., Al-Lehebi, Riyad, Rhee, Chin Kook, Perez-de-Llano, Luis, Perng Steve, Diahn Warng, Mahboub, Bassam, Wang, Eileen, Goh, Celine, Lyu, Juntao, Newell, Anthony, Alacqua, Marianna, Belevskiy, Andrey S., Bhutani, Mohit, Bjermer, Leif, Bjornsdottir, Unnur, Bourdin, Arnaud, Bulow, Anna von, Busby, John, Canonica, Giorgio Walter, Cosio, Borja G., Dorscheid, Delbert R., Muñoz-Esquerre, Mariana, FitzGerald, J. Mark, Gil, Esther Garcia, Gibson, Peter G., Heaney, Liam G., Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Jackson, David J., Koh, Mariko Siyue, Ko, Hsin Kuo Bruce, Lee, Jae Ha, Lehmann, Sverre, Chaves Loureiro, Cláudia, Lúðvíksdóttir, Dóra, Menzies-Gow, Andrew N., Mitchell, Patrick, Papaioannou, Andriana I., Popov, Todor A., Porsbjerg, Celeste M., Salameh, Laila, Sirena, Concetta, Taillé, Camille, Taube, Christian, Tohda, Yuji, Wechsler, Michael E., and Price, David B.

Abstract

Background Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. Results In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use., Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. Results: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). Conclusions: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.

Published
2023

28. Diabetes insipidus and Guillain-Barré-like syndrome following CAR-T cell therapy: a case report

Author

Koch, Christian, Fleischer, Juliane, Popov, Todor, Frontzek, Karl, Schreiner, Bettina, Roth, Patrick, Manz, Markus G, Unseld, Simone, Müller, Antonia M S; https://orcid.org/0000-0003-4420-9466, Russkamp, Norman F; https://orcid.org/0000-0002-3090-7186, Koch, Christian, Fleischer, Juliane, Popov, Todor, Frontzek, Karl, Schreiner, Bettina, Roth, Patrick, Manz, Markus G, Unseld, Simone, Müller, Antonia M S; https://orcid.org/0000-0003-4420-9466, and Russkamp, Norman F; https://orcid.org/0000-0002-3090-7186

Abstract

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited. Main body: We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months. Conclusions: This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.

Published
2023

29. Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination:Results of the UCARE COVAC-CU study

Author

Kocatürk, Emek, Salameh, Pascale, Sarac, Esra, Vera Ayala, Carolina E., Thomsen, Simon Francis, Zuberbier, Torsten, Ensina, Luis Felipe, Popov, Todor A., van Doorn, Martijn B.A., Giménez-Arnau, Ana Maria, Asero, Riccardo, Criado, Paulo Ricardo, Aarestrup, Fernando M., AbdulHameed Ansari, Zainab, Al Abri, Salma, Al Ahmad, Mona, Al Hinai, Bushra, Allenova, Anastasiia, Al-Nesf, Maryam, Altrichter, Sabine, Arnaout, Rand, Bartosińska, Joanna, Bauer, Andrea, Bernstein, Jonathan A., Bizjak, Mojca, Bonnekoh, Hanna, Bouillet, Laurence, Brzoza, Zenon, Calvalcanti Dela Bianca Melo, Ana Caroline, Campinhos, Fernanda L., Carne, Emily, Purayil, Saleema Cherichi, Cherrez-Ojeda, Ivan, Chong-Neto, Herberto Jose, Christoff, George, Conlon, Niall, Jardim Criado, Roberta Fachini, Cvenkel, Klara, Damadoglu, Ebru, Danilycheva, Inna, Day, Cascia, de Montjoye, Laurence, Demir, Semra, Ferucci, Silvia Mariel, Fomina, Daria, Fukunaga, Atsushi, Garcia, Elizabeth, Gelincik, Asli, Göbel, Joe Hannah, Godse, Kiran, Gonçalo, Margarida, Gotua, Maia, Grattan, Clive, Gugala, Agata, Guillet, Carole, Kalyoncu, Ali Fuat, Karakaya, Gul, Kasperska-Zając, Alicja, Katelaris, Constance H., Khoshkhui, Maryam, Kleinheinz, Andreas, Kolacinska-Flont, Marta, Kolkhir, Pavel, Košnik, Mitja, Krasowska, Dorota, Kumaran, Muthu Sendhil, Kuprys-Lipinska, Izabela, Kurowski, Marcin, Kuznetsova, Elizaveta V., Larenas-Linnemann, Désirée, Lebedkina, Marina S., Lee, Youngsoo, Makris, Michael P., Gómez, René Maximiliano, Nasr, Iman, Neisinger, Sophia, Oda, Yoshiko, Kara, Rabia Öztaş, Palitot, Esther Bastos, Papapostolou, Niki, Salvador Parisi, Claudio Alberto, Pesque, David, Peter, Jonathan, Petkova, Elena, Ridge, Katie, Rudenko, Michael, Rutkowski, Krzysztof, Saini, Sarbjit S., Salman, Andac, Sanchez, Jorge, Şekerel, Bülent, Serdotetskova, Sofia A., Serpa, Faradiba S., Dikicier, Bahar Sevimli, Sidiropoulos, Nikitas, Sikora, Agnieszka, Sørensen, Jennifer Astrup, Soria, Angele, Kucuk, Ozlem Su, Thalappil, Sherin Rahim, Tomaszewska, Katarzyna, Tuncay, Gulseren, Unal, Derya, Valle, Solange, van Lindonk, Esmee, Vestergaard, Christian, Vitchuk, Aleksandr, Xepapadaki, Paraskevi, Ye, Young Min, Zalewska-Janowska, Anna, Zamlynski, Mateusz, Maurer, Marcus, Kocatürk, Emek, Salameh, Pascale, Sarac, Esra, Vera Ayala, Carolina E., Thomsen, Simon Francis, Zuberbier, Torsten, Ensina, Luis Felipe, Popov, Todor A., van Doorn, Martijn B.A., Giménez-Arnau, Ana Maria, Asero, Riccardo, Criado, Paulo Ricardo, Aarestrup, Fernando M., AbdulHameed Ansari, Zainab, Al Abri, Salma, Al Ahmad, Mona, Al Hinai, Bushra, Allenova, Anastasiia, Al-Nesf, Maryam, Altrichter, Sabine, Arnaout, Rand, Bartosińska, Joanna, Bauer, Andrea, Bernstein, Jonathan A., Bizjak, Mojca, Bonnekoh, Hanna, Bouillet, Laurence, Brzoza, Zenon, Calvalcanti Dela Bianca Melo, Ana Caroline, Campinhos, Fernanda L., Carne, Emily, Purayil, Saleema Cherichi, Cherrez-Ojeda, Ivan, Chong-Neto, Herberto Jose, Christoff, George, Conlon, Niall, Jardim Criado, Roberta Fachini, Cvenkel, Klara, Damadoglu, Ebru, Danilycheva, Inna, Day, Cascia, de Montjoye, Laurence, Demir, Semra, Ferucci, Silvia Mariel, Fomina, Daria, Fukunaga, Atsushi, Garcia, Elizabeth, Gelincik, Asli, Göbel, Joe Hannah, Godse, Kiran, Gonçalo, Margarida, Gotua, Maia, Grattan, Clive, Gugala, Agata, Guillet, Carole, Kalyoncu, Ali Fuat, Karakaya, Gul, Kasperska-Zając, Alicja, Katelaris, Constance H., Khoshkhui, Maryam, Kleinheinz, Andreas, Kolacinska-Flont, Marta, Kolkhir, Pavel, Košnik, Mitja, Krasowska, Dorota, Kumaran, Muthu Sendhil, Kuprys-Lipinska, Izabela, Kurowski, Marcin, Kuznetsova, Elizaveta V., Larenas-Linnemann, Désirée, Lebedkina, Marina S., Lee, Youngsoo, Makris, Michael P., Gómez, René Maximiliano, Nasr, Iman, Neisinger, Sophia, Oda, Yoshiko, Kara, Rabia Öztaş, Palitot, Esther Bastos, Papapostolou, Niki, Salvador Parisi, Claudio Alberto, Pesque, David, Peter, Jonathan, Petkova, Elena, Ridge, Katie, Rudenko, Michael, Rutkowski, Krzysztof, Saini, Sarbjit S., Salman, Andac, Sanchez, Jorge, Şekerel, Bülent, Serdotetskova, Sofia A., Serpa, Faradiba S., Dikicier, Bahar Sevimli, Sidiropoulos, Nikitas, Sikora, Agnieszka, Sørensen, Jennifer Astrup, Soria, Angele, Kucuk, Ozlem Su, Thalappil, Sherin Rahim, Tomaszewska, Katarzyna, Tuncay, Gulseren, Unal, Derya, Valle, Solange, van Lindonk, Esmee, Vestergaard, Christian, Vitchuk, Aleksandr, Xepapadaki, Paraskevi, Ye, Young Min, Zalewska-Janowska, Anna, Zamlynski, Mateusz, and Maurer, Marcus

Abstract

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Results: Across 2769 COVID-19–vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination–induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination–induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine–related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. Conclusions: COVID-19 vaccination lead

Published
2023

30. Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization

Author

D’Amato, Gennaro, Holgate, Stephen T., Pawankar, Ruby, Ledford, Dennis K., Cecchi, Lorenzo, Al-Ahmad, Mona, Al-Enezi, Fatma, Al-Muhsen, Saleh, Ansotegui, Ignacio, Baena-Cagnani, Carlos E., Baker, David J., Bayram, Hasan, Bergmann, Karl Christian, Boulet, Louis-Philippe, Buters, Jeroen T.M., D’Amato, Maria, Dorsano, Sofia, Douwes, Jeroen, Finlay, Sarah Elise, Garrasi, Donata, Gómez, Maximiliano, Haahtela, Tari, Halwani, Rabih, Hassani, Youssouf, Mahboub, Basam, Marks, Guy, Michelozzi, Paola, Montagni, Marcello, Nunes, Carlos, Oh, Jay Jae-Won, Popov, Todor A., Portnoy, Jay, Ridolo, Erminia, Rosário, Nelson, Rottem, Menachem, Sánchez-Borges, Mario, Sibanda, Elopy, Sienra-Monge, Juan José, Vitale, Carolina, and Annesi-Maesano, Isabella

Published
2015
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34. Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy

Author

Chen, Wenjia, primary, Sadatsafavi, Mohsen, additional, Tran, Trung N, additional, Murray, Ruth B, additional, Wong, Chong Boon Nigel, additional, Ali, Nasloon, additional, Ariti, Cono, additional, Garcia Gil, Esther, additional, Newell, Anthony, additional, Alacqua, Marianna, additional, Al-Ahmad, Mona, additional, Altraja, Alan, additional, Al-Lehebi, Riyad, additional, Bhutani, Mohit, additional, Bjermer, Leif, additional, Bjerrum, Anne Sofie, additional, Bourdin, Arnaud, additional, Bulathsinhala, Lakmini, additional, von Bülow, Anna, additional, Busby, John, additional, Canonica, Giorgio Walter, additional, Carter, Victoria, additional, Christoff, George C, additional, Cosio, Borja G, additional, Costello, Richard W, additional, FitzGerald, J Mark, additional, Fonseca, João A, additional, Yoo, Kwang Ha, additional, Heaney, Liam G, additional, Heffler, Enrico, additional, Hew, Mark, additional, Hilberg, Ole, additional, Hoyte, Flavia, additional, Iwanaga, Takashi, additional, Jackson, David J, additional, Jones, Rupert C, additional, Koh, Mariko Siyue, additional, Kuna, Piotr, additional, Larenas-Linnemann, Désirée, additional, Lehmann, Sverre, additional, Lehtimäki, Lauri A, additional, Lyu, Juntao, additional, Mahboub, Bassam, additional, Maspero, Jorge, additional, Menzies-Gow, Andrew N, additional, Sirena, Concetta, additional, Papadopoulos, Nikolaos, additional, Papaioannou, Andriana I, additional, Pérez de Llano, Luis, additional, Perng, Diahn-Warng, additional, Peters, Matthew, additional, Pfeffer, Paul E, additional, Porsbjerg, Celeste M, additional, Popov, Todor A, additional, Rhee, Chin Kook, additional, Salvi, Sundeep, additional, Taillé, Camille, additional, Taube, Christian, additional, Torres-Duque, Carlos A, additional, Ulrik, Charlotte S, additional, Ra, Seung Won, additional, Wang, Eileen, additional, Wechsler, Michael E, additional, and Price, David B, additional

Published
2022
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36. The Allergen Immunotherapy Adverse Events Registry: Setup & methodology of a European Academy of Allergy and Clinical Immunology taskforce project.

Author

Asllani, Julijana, Mitsias, Dimitrios, Konstantinou, George, Priftanji, Alfred, Hoxha, Mehmet, Sinani, Gerta, Christoff, George, Zlatko, Dimitrov, Makris, Michael, Aggelidis, Xenofon, Stipic, Asja, Popovic‐Grle, Sanja, Deleanu, Diana, Tomic‐Spiric, Vesna, Plavsic, Aleksandra, Mungan, Dilsad, Kosnik, Mitja, Popov, Todor A., Papadopoulos, Nikolaos G., and Calderon, Moises

Subjects
CLINICAL immunology, ALLERGENS, ITCHING, ALLERGIES, DEGLUTITION, VENOM hypersensitivity, MEDICAL terminology
Abstract

To the Editor, Over the last decades, systematic reviews and meta analyses of multiple double-blind randomized placebo-controlled trials have demonstrated the efficacy and safety of both subcutaneous (SCIT) and sublingual (SLIT) allergen immunotherapy (AIT) for respiratory and insect venom allergy.[1] However, there is a wide range of AIT preparations used around the globe, and AEs are not always uniformly recorded, limiting the capability to draw safe conclusions or compare reports. Though various clinical development programs[2] have generated substantial knowledge on different AIT preparations, they have been conducted in pre-defined clinical conditions, not reflecting real-life and therefore the results may not have generalized applicability.[3] Very few pragmatic trials and observational studies have evaluated AIT safety in real-life. Adverse Events Registry is the first AIT Registry for AE piloted in different countries in Europe that uses the harmonized MedDRA terminology[9] (Table 1). [Extracted from the article]

Published
2023
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37. Adverse events in children and adolescents undergoing allergen immunotherapy for respiratory allergies—Report from the Allergen Immunotherapy Adverse Events Registry (ADER), a European Academy of Allergy and Clinical Immunology taskforce.

Author

Asllani, Julijana, Mitsias, Dimitrios, Konstantinou, George, Mesonjesi, Eris, Xhixha, Fatmira, Shehu, Esmeralda, Christoff, George, Noleva, Katia, Makris, Michael, Aggelidis, Xenofon, Turkalj, Mirjana, Damir, Erceg, Agache, Ioana, Tomic‐Spiric, Vesna, Stosovic, Rajica, Misirligil, Zeynep, Kosnik, Mitja, Popov, Todor A., Calderon, Moises, and Papadopoulos, Nikolaos G.

Subjects
RESPIRATORY allergy, CLINICAL immunology, ALLERGENS, IMMUNOTHERAPY, ALLERGIES
Abstract

Background: Although it has been shown that allergen immunotherapy (AIT) is well‐tolerated in children, systematic and prospective surveillance of AIT safety in real life settings is needed. Methods: The multinational Allergen Immunotherapy Adverse Events Registry (ADER) was designed to address AIT safety in real life clinical practice. Data on children ≤18 years old with respiratory allergies undergoing AIT were retrieved. Patient‐ and AIT‐related features were collected and analyzed. The characteristics of adverse events (AE) and risk factors were evaluated. Results: A total of 851 patients, 11.3 ± 3.4 years old, with rhinitis only (47.6%); asthma and rhinitis (44.5%); asthma (7.9%), receiving 998 AIT courses were analyzed. Sublingual immunotherapy (SLIT) accounted for 51% of the courses. In 84.5% of patients only one AIT treatment was prescribed. Pollen was the most frequent sensitizer (57.1%), followed by mites (53.4%), molds (18.2%) and epithelia (16.7%). Local and systemic AEs were reported in 85 patients (9.9%). Most AEs (83.1%) were mild and occurred in <30 min (87%). Respiratory and cutaneous symptoms were more frequent. Only 4 patients (0.47%) had severe AE (none after 6 weeks of maintenance). The risk of AE was higher in patients undergoing SCIT. Conclusions: AIT is safe and well tolerated in children and adolescents with respiratory allergies in real‐life clinical practice. Though SCIT is more prone to AE compared to SLIT, overall severe reactions are rare and occur during build‐up and early maintenance. [ABSTRACT FROM AUTHOR]

Published
2023
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39. In vitro and in vivo Evaluation of the Efficacy and Safety of Powder Hydroxypropylmethylcellulose as Nasal Mucosal Barrier

Author

Popov, Todor A, Emberlin, Jean, Josling, Peter, and Seifalian, Alexander

Subjects
micronized powder, inhaled allergens, particulate matter 2.5, hydroxypropylmethylcellulose, HPMC, safety in rats, PM2.5, allergen barrier, cellulose, Original Research
Abstract

Introduction Insufflation of powder hydroxypropylmethylcellulose (pHPMC) in the nose has been proven an effective barrier in subjects with rhinitis in many clinical studies. We conducted additionally in vitro and in vivo experiments to address outstanding efficacy and safety issues. Methods We used an experimental setup to demonstrate the inhibition of the diffusion of allergen extracts (house dust mite, Japanese cedar, Ragweed, Timothy grass) and pollutants (particulate matter 2.5 µm, PM2.5). Safety of pHPMC when insufflated in the airways of rats was assessed in 24 animals which were sacrificed; tissue sections from lungs, brain and liver were made 1, 24 and 48 hrs after pHPMC inhalation and compared to those of control animals. Results pHPMC acted as an effective barrier to diffusion of both the liquid allergen extracts and of PM2.5 into the agar covered slides: the quantities of the other tested allergens ranged between

Published
2020

40. Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy

Author

Chen, Wenjia, Sadatsafavi, Mohsen, Tran, Trung N., Murray, Ruth B., Wong, Chong Boon Nigel, Ali, Nasloon, Ariti, Cono, Gil, Esther Garcia, Newell, Anthony, Alacqua, Marianna, Al-Ahmad, Mona, Altraja, Alan, Al-Lehebi, Riyad, Bhutani, Mohit, Bjermer, Leif, Bjerrum, Anne Sofie, Bourdin, Arnaud, Bulathsinhala, Lakmini, Von Bülow, Anna, Busby, John, Canonica, Giorgio Walter, Carter, Victoria, Christoff, George C., Cosio, Borja G., Costello, Richard W., Fitzgerald, J. Mark, Fonseca, João A., Ha Yoo, Kwang, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Iwanaga, Takashi, Jackson, David J., Jones, Rupert C., Koh, Mariko Siyue, Kuna, Piotr, Larenas-Linnemann, Désirée, Lehmann, Sverre, Lehtimäki, Lauri A., Lyu, Juntao, Mahboub, Bassam, Maspero, Jorge, Menzies-Gow, Andrew N., Sirena, Concetta, Papadopoulos, Nikolaos, Papaioannou, Andriana I., De Llano, Luis Pérez, Perng, Diahn Warng, Peters, Matthew, Pfeffer, Paul E., Porsbjerg, Celeste M., Popov, Todor A., Rhee, Chin Kook, Salvi, Sundeep, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte S., Won Ra, Seung, Wang, Eileen, Wechsler, Michael E., Price, David B., Chen, Wenjia, Sadatsafavi, Mohsen, Tran, Trung N., Murray, Ruth B., Wong, Chong Boon Nigel, Ali, Nasloon, Ariti, Cono, Gil, Esther Garcia, Newell, Anthony, Alacqua, Marianna, Al-Ahmad, Mona, Altraja, Alan, Al-Lehebi, Riyad, Bhutani, Mohit, Bjermer, Leif, Bjerrum, Anne Sofie, Bourdin, Arnaud, Bulathsinhala, Lakmini, Von Bülow, Anna, Busby, John, Canonica, Giorgio Walter, Carter, Victoria, Christoff, George C., Cosio, Borja G., Costello, Richard W., Fitzgerald, J. Mark, Fonseca, João A., Ha Yoo, Kwang, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Hilberg, Ole, Hoyte, Flavia, Iwanaga, Takashi, Jackson, David J., Jones, Rupert C., Koh, Mariko Siyue, Kuna, Piotr, Larenas-Linnemann, Désirée, Lehmann, Sverre, Lehtimäki, Lauri A., Lyu, Juntao, Mahboub, Bassam, Maspero, Jorge, Menzies-Gow, Andrew N., Sirena, Concetta, Papadopoulos, Nikolaos, Papaioannou, Andriana I., De Llano, Luis Pérez, Perng, Diahn Warng, Peters, Matthew, Pfeffer, Paul E., Porsbjerg, Celeste M., Popov, Todor A., Rhee, Chin Kook, Salvi, Sundeep, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte S., Won Ra, Seung, Wang, Eileen, Wechsler, Michael E., and Price, David B.

Abstract

Background: Many severe asthma patients with high oral corticosteroid exposure (HOCS) often do not initiate biologics despite being eligible. This study aimed to compare the characteristics of severe asthma patients with HOCS who did and did not initiate biologics. Methods: Baseline characteristics of patients with HOCS (long-term maintenance OCS therapy for at least 1 year, or ≥4 courses of steroid bursts in a year) from the International Severe Asthma Registry (ISAR; https://isaregistries.org/), who initiated or did not initiate biologics (anti-lgE, anti-IL5/5R or anti-IL4R), were described at the time of biologic initiation or registry enrolment. Statistical relationships were tested using Pearson's chi-squared tests for categorical variables, and t-tests for continuous variables, adjusting for potential errors in multiple comparisons. Results: Between January 2015 and February 2021, we identified 1412 adult patients with severe asthma from 19 countries that met our inclusion criteria of HOCS, of whom 996 (70.5%) initiated a biologic and 416 (29.5%) did not. The frequency of biologic initiation varied across geographical regions. Those who initiated a biologic were more likely to have higher blood eosinophil count (483 vs 399 cells/µL, p=0.003), serious infections (49.0% vs 13.3%, p<0.001), nasal polyps (35.2% vs 23.6%, p<0.001), airflow limitation (56.8% vs 51.8%, p=0.013), and uncontrolled asthma (80.8% vs 73.2%, p=0.004) despite greater conventional treatment adherence than those who did not start a biologic. Both groups had similar annual asthma exacerbation rates in the previous 12 months (5.7 vs 5.3, p=0.147). Conclusion: Around one third of severe HOCS asthma patients did not receive biologics despite a similar high burden of asthma exacerbations as those who initiated a biologic therapy. Other disease characteristics such as eosinophilic phenotype, serious infectious events, nasal polyps, airflow limitation and lack of asthma control appear to di

Published
2022

41. Characterization of Patients in the International Severe Asthma Registry with High Steroid Exposure Who Did or Did Not Initiate Biologic Therapy

Author

Chen,Wenjia, Sadatsafavi,Mohsen, Tran,Trung N, Murray,Ruth B, Wong,Chong Boon Nigel, Ali,Nasloon, Ariti,Cono, Garcia Gil,Esther, Newell,Anthony, Alacqua,Marianna, Al-Ahmad,Mona, Altraja,Alan, Al-Lehebi,Riyad, Bhutani,Mohit, Bjermer,Leif, Bjerrum,Anne Sofie, Bourdin,Arnaud, Bulathsinhala,Lakmini, von Bülow,Anna, Busby,John, Canonica,Giorgio Walter, Carter,Victoria, Christoff,George C, Cosio,Borja G, Costello,Richard W, FitzGerald,J Mark, Fonseca,João A, Yoo,Kwang Ha, Heaney,Liam G, Heffler,Enrico, Hew,Mark, Hilberg,Ole, Hoyte,Flavia, Iwanaga,Takashi, Jackson,David J, Jones,Rupert C, Koh,Mariko Siyue, Kuna,Piotr, Larenas-Linnemann,Désirée, Lehmann,Sverre, Lehtimäki,Lauri A, Lyu,Juntao, Mahboub,Bassam, Maspero,Jorge, Menzies-Gow,Andrew N, Sirena,Concetta, Papadopoulos,Nikolaos, Papaioannou,Andriana I, Pérez de Llano,Luis, Perng,Diahn-Warng, Peters,Matthew, Pfeffer,Paul E, Porsbjerg,Celeste M, Popov,Todor A, Rhee,Chin Kook, Salvi,Sundeep, Taillé,Camille, Taube,Christian, Torres-Duque,Carlos A, Ulrik,Charlotte S, Ra,Seung Won, Wang,Eileen, Wechsler,Michael E, Price,David B, Chen,Wenjia, Sadatsafavi,Mohsen, Tran,Trung N, Murray,Ruth B, Wong,Chong Boon Nigel, Ali,Nasloon, Ariti,Cono, Garcia Gil,Esther, Newell,Anthony, Alacqua,Marianna, Al-Ahmad,Mona, Altraja,Alan, Al-Lehebi,Riyad, Bhutani,Mohit, Bjermer,Leif, Bjerrum,Anne Sofie, Bourdin,Arnaud, Bulathsinhala,Lakmini, von Bülow,Anna, Busby,John, Canonica,Giorgio Walter, Carter,Victoria, Christoff,George C, Cosio,Borja G, Costello,Richard W, FitzGerald,J Mark, Fonseca,João A, Yoo,Kwang Ha, Heaney,Liam G, Heffler,Enrico, Hew,Mark, Hilberg,Ole, Hoyte,Flavia, Iwanaga,Takashi, Jackson,David J, Jones,Rupert C, Koh,Mariko Siyue, Kuna,Piotr, Larenas-Linnemann,Désirée, Lehmann,Sverre, Lehtimäki,Lauri A, Lyu,Juntao, Mahboub,Bassam, Maspero,Jorge, Menzies-Gow,Andrew N, Sirena,Concetta, Papadopoulos,Nikolaos, Papaioannou,Andriana I, Pérez de Llano,Luis, Perng,Diahn-Warng, Peters,Matthew, Pfeffer,Paul E, Porsbjerg,Celeste M, Popov,Todor A, Rhee,Chin Kook, Salvi,Sundeep, Taillé,Camille, Taube,Christian, Torres-Duque,Carlos A, Ulrik,Charlotte S, Ra,Seung Won, Wang,Eileen, Wechsler,Michael E, and Price,David B

Abstract

Wenjia Chen,1 Mohsen Sadatsafavi,2 Trung N Tran,3 Ruth B Murray,4 Chong Boon Nigel Wong,1 Nasloon Ali,4,5 Cono Ariti,4,5 Esther Garcia Gil,6 Anthony Newell,5,7 Marianna Alacqua,8 Mona Al-Ahmad,9 Alan Altraja,10 Riyad Al-Lehebi,11,12 Mohit Bhutani,13 Leif Bjermer,14 Anne Sofie Bjerrum,15 Arnaud Bourdin,16 Lakmini Bulathsinhala,4,5 Anna von Bülow,17 John Busby,18 Giorgio Walter Canonica,19,20 Victoria Carter,4,5 George C Christoff,21 Borja G Cosio,22 Richard W Costello,23 J Mark FitzGerald,24 João A Fonseca,25 Kwang Ha Yoo,26 Liam G Heaney,27 Enrico Heffler,19,20 Mark Hew,28,29 Ole Hilberg,30 Flavia Hoyte,31,32 Takashi Iwanaga,33 David J Jackson,34,35 Rupert C Jones,36 Mariko Siyue Koh,37,38 Piotr Kuna,39 Désirée Larenas-Linnemann,40 Sverre Lehmann,41 Lauri A Lehtimäki,42,43 Juntao Lyu,5,7 Bassam Mahboub,44,45 Jorge Maspero,46,47 Andrew N Menzies-Gow,48 Concetta Sirena,49 Nikolaos Papadopoulos,50,51 Andriana I Papaioannou,52 Luis Pérez de Llano,53,54 Diahn-Warng Perng,55,56 Matthew Peters,57 Paul E Pfeffer,58,59 Celeste M Porsbjerg,17 Todor A Popov,60 Chin Kook Rhee,61 Sundeep Salvi,62 Camille Taillé,63 Christian Taube,64 Carlos A Torres-Duque,65 Charlotte S Ulrik,66 Seung Won Ra,67 Eileen Wang,31,32 Michael E Wechsler,68 David B Price4,5,69 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore; 2Respiratory Evaluation Sciences Program, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 3AstraZeneca, Gaithersburg, MD, USA; 4Optimum Patient Care, Cambridge, UK; 5Observational and Pragmatic Research Institute, Singapore, Singapore; 6AstraZeneca, Barcelona, Spain; 7Optimum Patient Care, Queensland, VIC, Australia; 8AstraZeneca, Cambridge, UK; 9Microbiology Department, Faculty of Medicine, Kuwait University, Al-Rashed Allergy Center, Ministry of Health, Kuwait City, Kuwait; 10Department of Pulmonology, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia; 11De

Published
2022

42. Development and validation of the Food Allergy Severity Score

Author

Fernández-Rivas, Montserrat, Gómez García, Ismael, Gonzalo-Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle-Bierke, Sabine, Marco-Martín, Guadalupe, Ballmer-Weber, Barbara K, Asero, Riccardo, Belohlavkova, Simona, Beyer, Kirsten, de Blay, Frédéric, Clausen, Michael, Datema, Mareen R, Dubakiene, Ruta, Grimshaw, Kate E C, Hoffmann-Sommergruber, Karin, Hourihane, Jonathan O'B, Jedrzejczak-Czechowicz, Monika, Knulst, André C, Kralimarkova, Tanya, Le, Thuy-My, Papadopoulos, Nikolaos G, Popov, Todor A, Poulsen, Lars K, Purohit, Ashok, Seneviratne, Suranjith L, Simpson, Angela, Sinaniotis, Atanasios, Turkalji, Mirjana, Vázquez-Cortés, Sonia, Vera-Berrios, Rosialzira N, Muraro, Antonella, Worm, Margitta, Roberts, Graham, van Ree, Ronald, Fernández-Pérez, Cristina, Turner, Paul J, Mills, Elizabeth N Clare, Fernández-Rivas, Montserrat, Gómez García, Ismael, Gonzalo-Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle-Bierke, Sabine, Marco-Martín, Guadalupe, Ballmer-Weber, Barbara K, Asero, Riccardo, Belohlavkova, Simona, Beyer, Kirsten, de Blay, Frédéric, Clausen, Michael, Datema, Mareen R, Dubakiene, Ruta, Grimshaw, Kate E C, Hoffmann-Sommergruber, Karin, Hourihane, Jonathan O'B, Jedrzejczak-Czechowicz, Monika, Knulst, André C, Kralimarkova, Tanya, Le, Thuy-My, Papadopoulos, Nikolaos G, Popov, Todor A, Poulsen, Lars K, Purohit, Ashok, Seneviratne, Suranjith L, Simpson, Angela, Sinaniotis, Atanasios, Turkalji, Mirjana, Vázquez-Cortés, Sonia, Vera-Berrios, Rosialzira N, Muraro, Antonella, Worm, Margitta, Roberts, Graham, van Ree, Ronald, Fernández-Pérez, Cristina, Turner, Paul J, and Mills, Elizabeth N Clare

Abstract

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions.METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated.RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians.CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

Published
2022

43. Development and validation of the Food Allergy Severity Score

Author

MS Dermatologie/Allergologie, Infection & Immunity, Fernández-Rivas, Montserrat, Gómez García, Ismael, Gonzalo-Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle-Bierke, Sabine, Marco-Martín, Guadalupe, Ballmer-Weber, Barbara K., Asero, Riccardo, Belohlavkova, Simona, Beyer, Kirsten, de Blay, Frédéric, Clausen, Michael, Datema, Mareen R., Dubakiene, Ruta, Grimshaw, Kate E.C., Hoffmann-Sommergruber, Karin, Hourihane, Jonathan O.B., Jedrzejczak-Czechowicz, Monika, Knulst, André C., Kralimarkova, Tanya, Le, Thuy My, Papadopoulos, Nikolaos G., Popov, Todor A., Poulsen, Lars K., Purohit, Ashok, Seneviratne, Suranjith L., Simpson, Angela, Sinaniotis, Atanasios, Turkalji, Mirjana, Vázquez-Cortés, Sonia, Vera-Berrios, Rosialzira N., Muraro, Antonella, Worm, Margitta, Roberts, Graham, van Ree, Ronald, Fernández-Pérez, Cristina, Turner, Paul J., Mills, Elizabeth N.Clare, MS Dermatologie/Allergologie, Infection & Immunity, Fernández-Rivas, Montserrat, Gómez García, Ismael, Gonzalo-Fernández, Alejandro, Fuentes Ferrer, Manuel, Dölle-Bierke, Sabine, Marco-Martín, Guadalupe, Ballmer-Weber, Barbara K., Asero, Riccardo, Belohlavkova, Simona, Beyer, Kirsten, de Blay, Frédéric, Clausen, Michael, Datema, Mareen R., Dubakiene, Ruta, Grimshaw, Kate E.C., Hoffmann-Sommergruber, Karin, Hourihane, Jonathan O.B., Jedrzejczak-Czechowicz, Monika, Knulst, André C., Kralimarkova, Tanya, Le, Thuy My, Papadopoulos, Nikolaos G., Popov, Todor A., Poulsen, Lars K., Purohit, Ashok, Seneviratne, Suranjith L., Simpson, Angela, Sinaniotis, Atanasios, Turkalji, Mirjana, Vázquez-Cortés, Sonia, Vera-Berrios, Rosialzira N., Muraro, Antonella, Worm, Margitta, Roberts, Graham, van Ree, Ronald, Fernández-Pérez, Cristina, Turner, Paul J., and Mills, Elizabeth N.Clare

Published
2022

45. Exhaled Breath Temperature Home Monitoring to Detect NSCLC Relapse: Results from a Pilot Study

Author

Carpagnano, Giovanna Elisiana, primary, Popov, Todor A., additional, Scioscia, Giulia, additional, Ardò, Nicoletta Pia, additional, Lacedonia, Donato, additional, Malerba, Mario, additional, Tondo, Pasquale, additional, Soccio, Piera, additional, Loizzi, Domenico, additional, Foschino Barbaro, Maria Pia, additional, and Sollitto, Francesco, additional

Published
2022
Full Text
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47. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Porsbjerg, Celeste M., Menzies-Gow, Andrew N., Tran, Trung N., Murray, Ruth B., Unni, Bindhu, Audrey Ang, Shi Ling, Alacqua, Marianna, Al-Ahmad, Mona, Al-Lehebi, Riyad, Altraja, Alan, Belevskiy, Andrey S., Björnsdóttir, Unnur S., Bourdin, Arnaud, Busby, John, Canonica, G. Walter, Christoff, George C., Cosio, Borja G., Costello, Richard W., FitzGerald, J. Mark, Fonseca, João A., Hansen, Susanne, Heaney, Liam G., Heffler, Enrico, Hew, Mark, Iwanaga, Takashi, Jackson, Daniel J., Kocks, Janwillem W.H., Kallieri, Maria, Bruce Ko, Hsin Kuo, Koh, Mariko Siyue, Larenas-Linnemann, Désirée, Lehtimäki, Lauri A., Loukides, Stelios, Lugogo, Njira, Maspero, Jorge, Papaioannou, Andriana I., Perez-de-Llano, Luis, Pitrez, Paulo Márcio, Popov, Todor A., Rasmussen, Linda M., Rhee, Chin Kook, Sadatsafavi, Mohsen, Schmid, Johannes, Siddiqui, Salman, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos A., Ulrik, Charlotte, Upham, John W., Wang, Eileen, Wechsler, Michael E., Bulathsinhala, Lakmini, Carter, Victoria, Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Rowlands, Mari Anne, Price, David B., van Boven, Job F.M., Tampere University, Department of Respiratory medicine, Dermatology and Allergology, and Clinical Medicine

Subjects
3121 Internal medicine
Abstract

Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. Objective: To compare global differences in ease of access to biologics. Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world. publishedVersion

Published
2022

48. Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort

Author

Heaney, Liam G., Perez de Llano, Luis, Al-Ahmad, Mona, Backer, Vibeke, Busby, John, Canonica, Giorgio Walter, Christoff, George C., Cosio, Borja G., FitzGerald, J. Mark, Heffler, Enrico, Iwanaga, Takashi, Jackson, David J., Menzies-Gow, Andrew N., Papadopoulos, Nikolaos G., Papaioannou, Andriana I., Pfeffer, Paul E., Popov, Todor A., Porsbjerg, Celeste M., Rhee, Chin Kook, Sadatsafavi, Mohsen, Tohda, Yuji, Wang, Eileen, Wechsler, Michael E., Alacqua, Marianna, Altraja, Alan, Bjermer, Leif, Björnsdóttir, Unnur S., Bourdin, Arnaud, Brusselle, Guy G., Buhl, Roland, Costello, Richard W., Hew, Mark, Koh, Mariko Siyue, Lehmann, Sverre, Lehtimäki, Lauri, Peters, Matthew, Taillé, Camille, Taube, Christian, Tran, Trung N., Zangrilli, James, Bulathsinhala, Lakmini, Carter, Victoria A., Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Kerkhof, Marjan, Murray, Ruth B., Price, Chris A., Price, David B., Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidemiology, Tampere University, Department of Respiratory medicine, Dermatology and Allergology, and Clinical Medicine

Subjects
PROTOCOL, Adult, Male, Asia, [SDV]Life Sciences [q-bio], Medizin, 3121 Internal medicine, Global Health, Severity of Illness Index, VALIDATION, International Severe Asthma Registry, MECHANISMS, Cohort Studies, Leukocyte Count, Middle East, Adrenal Cortex Hormones, Eosinophilia, Medicine and Health Sciences, Prevalence, Humans, Anti-Asthmatic Agents, Registries, Age of Onset, PREDICTORS, ComputingMilieux_MISCELLANEOUS, RECEPTOR, BENRALIZUMAB, Middle Aged, Asthma, Patient Care Management, Respiratory Function Tests, Eosinophils, Europe, Biological Variation, Population, North America, Female, FENO
Abstract

Background: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). Results: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. Interpretation: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision. publishedVersion

Published
2021
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49. ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Author

Bousquet, Jean, Pfaar, Oliver, Agache, Ioana, Bedbrook, Anna, Akdis, Cezmi A, Canonica, Giorgio Walter, Chivato, Tomas, Al-Ahmad, Mona, Rasib, A. H. Abdul, Ansotegui, Ignacio J, Bachert, Claus, Soto-Martinez, Manuel, Laune, Daniel, Casale, Tomas, Levin, Michael, Larenas-Linnemann, Désirée, Samolinski, Boleslaw, Lodrup Carlsen, Karin C, O'Mahony, Liam, Lombardi, Carlo, Riggioni, Carmen, Hossny, Elham, Barata, Luís Taborda, Lourenço, Olga, Devillier, Philippe, Mahboub, Bassam, Malling, Hans-Jørgen, Sheikh, Aziz, Manning, Patrick, Passalacqua, Giovanni, Marshall, Gailen D, Sanchez-Borges, Mario, Toppila-Salmi, Sanna, Melén, Erik, Fokkens, Wytske J, Meltzer, Eli O, Miculinic, Neven, Soto-Quiros, Manuel, Milenkovic, Branislava, Roberts, Graham, Ohta, Ken, Scichilone, Nicola, Moin, Mostafa, Odemyr, Mikaëla, Montefort, Stephen, Almeida, Mário Morais, Bom, Ana Todo, Mortz, Charlotte G, Serpa, Faradiba S, Patella, Vincenzo, Sova, Milan, Mösges, Ralph, Mullol, Joaquim, Namazova Baranova, Leyla, Tsiligianni, Ioanna, Neffen, Hugo, Bjermer, Leif, Rodriguez-Gonzales, Monica, Torres, Maria J, Okamoto, Yoshitaka, Okubo, Kimi, Pajno, Giovanni B, Baharuddin, Abdullah, Cecchi, Lorenzo, Sastre, Joaquin, Untersmayr, Eva, Pawankar, Ruby, Pham-Thi, Nhân, Plavec, Davor, Cardona, Victoria, Dokic, Dejan, Sisul, Juan Carlos, Rosario, Nelson, Rottem, Menachem, Rouadi, Philip W, Del Giacco, Stefano, Fonseca, Joao A, Schwarze, Jürgen, Scadding, Glenis K, Shamji, Mohamed H, Schmid-Grendelmeier, Peter, Niedoszytko, Marek, Valentin-Rostan, Marylin, Sofiev, Mikhail, Solé, Dirceu, Sooronbaev, Talant, Palkonen, Susanna, Urrutia-Pereira, Marilyn, Skypala, Isabel, Suppli-Ulrik, Charlotte, Bonini, Matteo, Popov, Todor A, Tomazic, Peter-Valentin, Valero, Antonio, Cepeda Sarabia, Alfonso M, Ryan, Dermot, Bosnic-Anticevich, Sinthia, Valiulis, Arunas, Durham, Stephen L, Schünemann, Holger, Kalayci, Omer, Valovirta, Erkka, Panzner, Petr, Vandenplas, Olivier, Ventura, Maria Teresa, Gotua, Maia, Vichyanond, Pakit, Chkhartishvili, Ekaterine, Wagenmann, Martin, Fontaine, Jean-François, Kull, Inger, Wallace, Dana, Recto, Marysia, Walusiak-Skorupa, Jolanta, Wang, De Yun, Hrubiško, Martin, Waserman, Susan, Ebisawa, Motohiro, Bosse, Isabelle, Grisle, Ineta, Wong, Gary Wk, Bindslev-Jensen, Carsten, Yorgancioglu, Arzu, Yusuf, Osman M, Khaitov, Musa, Zernotti, Mario, Gawlik, Radoslaw, Chu, Derek K, Irani, Carla, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Torsten, Kuna, Piotr, Jutel, Marek, Guzmán, Maria Antonieta, El-Gamal, Yehia, Klimek, Ludger, Brough, Helen A, Brussino, Luisa, Calderon, Moises A, Caraballo, Luis, O'Hehir, Robyn E, Gelincik, Asli, Kvedariene, Violeta, Cirule, Ieva, Cruz, Alvaro A, Czarlewski, Wienczyslawa, Nekam, Kristof, Papadopoulos, Nikolaos G., Haahtela, Tari, Emuzyte, Regina, Gamkrelidze, Amiran, Fauquert, Jean Luc, Palomares, Oscar, Regateiro, Frederico S, Ivancevich, Juan Carlos, Gemicioglu, Bilun, Gereda, Jose E, Gerth van Wijk, Roy, Bergmann, Karl-Christian, Knol, Edward, Halken, Susanne, Heffler, Enrico, Hoffmann-Sommergruber, Karin, Martins, Pedro Carreiro, Kritikos, Vicky, Ispayeva, Zhanat, Julge, Kaja, Kaidashev, Igor, Demoly, Pascal, Kowalski, Marek, Kraxner, Helga, Ollert, Markus, Fiocchi, Alessandro, Lauerma, Antti, Lau, Susanne, Park, Hae-Sim, Gomez, R Maximiliano, Comprehensive Health Research Centre (CHRC) - pólo NMS, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), uBibliorum, Bousquet J., Pfaar O., Agache I., Bedbrook A., Akdis C.A., Canonica G.W., Chivato T., Al-Ahmad M., Abdul Latiff A.H., Ansotegui I.J., Bachert C., Baharuddin A., Bergmann K.-C., Bindslev-Jensen C., Bjermer L., Bonini M., Bosnic-Anticevich S., Bosse I., Brough H.A., Brussino L., Calderon M.A., Caraballo L., Cardona V., Carreiro-Martins P., Casale T., Cecchi L., Cepeda Sarabia A.M., Chkhartishvili E., Chu D.K., Cirule I., Cruz A.A., Czarlewski W., del Giacco S., Demoly P., Devillier P., Dokic D., Durham S.L., Ebisawa M., El-Gamal✝ Y., Emuzyte R., Gamkrelidze A., Fauquert J.L., Fiocchi A., Fokkens W.J., Fonseca J.A., Fontaine J.-F., Gawlik R., Gelincik A., Gemicioglu B., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gotua M., Grisle I., Guzman M.-A., Haahtela T., Halken S., Heffler E., Hoffmann-Sommergruber K., Hossny E., Hrubisko M., Irani C., Ivancevich J.C., Ispayeva Z., Julge K., Kaidashev I., Kalayci O., Khaitov M., Klimek L., Knol E., Kowalski M.L., Kraxner H., Kull I., Kuna P., Kvedariene V., Kritikos V., Lauerma A., Lau S., Laune D., Levin M., Larenas-Linnemann D.E., Lodrup Carlsen K.C., Lombardi C., Lourenco O.M., Mahboub B., Malling H.-J., Manning P., Marshall G.D., Melen E., Meltzer E.O., Miculinic N., Milenkovic B., Moin M., Montefort S., Morais-Almeida M., Mortz C.G., Mosges R., Mullol J., Namazova Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Ollert M., O'Mahony L., Ohta K., Okamoto Y., Okubo K., Pajno G.B., Palomares O., Palkonen S., Panzner P., G Papadopoulos N., Park H.-S., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Plavec D., Popov T.A., Recto M., Regateiro F.S., Riggioni C., Roberts G., Rodriguez-Gonzales M., Rosario N., Rottem M., Rouadi P.W., Ryan D., Samolinski B., Sanchez-Borges✝ M., Serpa F.S., Sastre J., Scadding G.K., Shamji M.H., Schmid-Grendelmeier P., Schunemann H.J., Sheikh A., Scichilone N., Sisul J.C., Sofiev M., Sole D., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Sova M., Schwarze J., Skypala I., Suppli-Ulrik C., Taborda-Barata L., Todo-Bom A., Torres M.J., Valentin-Rostan M., Tomazic P.-V., Valero A., Toppila-Salmi S., Tsiligianni I., Untersmayr E., Urrutia-Pereira M., Valiulis A., Valovirta E., Vandenplas O., Ventura M.T., Vichyanond P., Wagenmann M., Wallace D., Walusiak-Skorupa J., Wang D.Y., Waserman S., Wong G.W.K., Yorgancioglu A., Yusuf O.M., Zernotti M., Zhang L., Zidarn M., Zuberbier T., Jutel M., HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Department of Pathology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Philipps Universität Marburg = Philipps University of Marburg, Transilvania University of Brasov, Universität Zürich [Zürich] = University of Zurich (UZH), Humanitas University [Milan] (Hunimed), Universidad San Pablo CEU, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Pantai Hospital [Kuala Lumpur], Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Sun Yat-Sen University [Guangzhou] (SYSU), Universiti Sains Malaysia (USM), Humboldt University Of Berlin, Berlin Institute of Health (BIH), Odense University Hospital (OUH), Skane University Hospital [Lund], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Woolcock Institute of Medical Research [Sydney], The University of Sydney, Guy's and St Thomas' Hospital [London], King‘s College London, Università degli studi di Torino = University of Turin (UNITO), University of Cartagena, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], Universidad Simon Bolivar (USB), David Tvildiani Medical University (DTMU), McMaster University [Hamilton, Ontario], Children's Clinical University Hospital [Riga, Latvia] (CCUH), Universidade Federal da Bahia (UFBA), Università degli Studi di Cagliari = University of Cagliari (UniCa), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Foch [Suresnes], Sagamihara National Hospital [Kanagawa, Japan], Université Ain Shams, Vilnius University [Vilnius], CHU Clermont-Ferrand, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Universidade do Porto = University of Porto, Silesian Medical University, Katowice, Poland, Cerrahpasa Faculty of Medicine, Istanbul University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Chile = University of Chile [Santiago] (UCHILE), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Medizinische Universität Wien = Medical University of Vienna, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Tartu University Hospital [Tartu, Estonia], Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Hacettepe University = Hacettepe Üniversitesi, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Nova Southeastern University (NSU), Nofer Institute of Occupational Medicine (NIOM), National University of Singapore (NUS), Yong Loo Lin School of Medicine [Singapore], The Chinese University of Hong Kong [Hong Kong], Manisa Celal Bayar University, Universidad Nacional de Villa María, Universidad Católica de Córdoba, Beijing Tongren Hospital, Herrada, Anthony, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie

Subjects
Pulmonary and Respiratory Medicine, precision medicine, education, Immunology, Review, Settore MED/10 - Malattie Dell'Apparato Respiratorio, immune system diseases, HDE ALER, allergic rhinitis, asthma, immunotherapy, Medicine and Health Sciences, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Rhinitis, RC581-607, respiratory tract diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunologic diseases. Allergy, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, allergic rhinitis, asthma, immunotherapy, precision medicine
Abstract

Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published

Published
2021
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50. Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma

Author

Meghoufel, Z, Cherifi, F, Boukra, A, Terki, F, Porsbjerg, Celeste, Menzies-Gow, Andrew, Tran, Trung, Murray, Ruth, Unni, Bindhu, Audrey Ang, Shi Ling, Alacqua, Marianna, Al-Ahmad, Mona, Al-Lehebi, Riyad, Altraja, Alan, Belevskiy, Andrey, Björnsdóttir, Unnur, Bourdin, Arnaud, Busby, John, Canonica, G. Walter, Christoff, George, Cosio, Borja, Costello, Richard, FitzGerald, J. Mark, Fonseca, João, Hansen, Susanne, Heaney, Liam, Heffler, Enrico, Hew, Mark, Iwanaga, Takashi, Jackson, David, Kocks, Janwillem W.H., Kallieri, Maria, Bruce Ko, Hsin-Kuo, Koh, Mariko Siyue, Larenas-Linnemann, Désirée, Lehtimäki, Lauri, Loukides, Stelios, Lugogo, Njira, Maspero, Jorge, Papaioannou, Andriana, Perez-de-Llano, Luis, Pitrez, Paulo Márcio, Popov, Todor, Rasmussen, Linda, Rhee, Chin Kook, Sadatsafavi, Mohsen, Schmid, Johannes, Siddiqui, Salman, Taillé, Camille, Taube, Christian, Torres-Duque, Carlos, Ulrik, Charlotte, Upham, John, Wang, Eileen, Wechsler, Michael, Bulathsinhala, Lakmini, Carter, Victoria, Chaudhry, Isha, Eleangovan, Neva, Hosseini, Naeimeh, Rowlands, Mari-Anne, Price, David, van Boven, Job FM., Groningen Research Institute for Asthma and COPD (GRIAC), Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Subjects
Severe asthma, Biological Products, [SDV]Life Sciences [q-bio], Medizin, Biologics access, Omalizumab, 3. Good health, Biologics eligibility, Biological Therapy, 03 medical and health sciences, BIOLOGICS, 0302 clinical medicine, Prescriptions, 030228 respiratory system, Immunology and Allergy, Humans, ASTHMA, 030212 general & internal medicine, Anti-Asthmatic Agents, ComputingMilieux_MISCELLANEOUS, SEVERE ASTHMA
Abstract

BackgroundRegulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine.ObjectiveTo compare global differences in ease of access to biologics.MethodsIn April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access.ResultsBiologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti–IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower.ConclusionsAlthough some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.

Published
2022
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