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1. Rhinitis associated with asthma is distinct from rhinitis alone:The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickman, M, Akdis, M, Aguilar, D, Bedbrook, A, Bindslev-Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia-Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makela, M, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Ansotegui, I J, Arshad, S H, Asayag, E, Barbara, C, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R S, Bush, A, Calderon, M, Calvo-Gil, M, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia de Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, A F, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Grutta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohammad, Y, Moniuszko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, M S, Robalo Cordeiro, C, Roche, N, Rodriguez-Gonzalez, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Serpa, F S, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, Van Ganse, E, van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases., Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Published
2023

2. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, Anto, J M, Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Aguilar, D, Akdis, M, Ansotegui, I J, Barbara, C, Bedbrook, A, Bindslev Jensen, C, Bosnic-Anticevich, S, Boulet, L P, Brightling, C E, Brussino, L, Burte, E, Bustamante, M, Canonica, G W, Cecchi, L, Celedon, J C, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, Michael, Blain, H, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Zuberbier, T, and Anto, J M

Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. [Abstract copyright: This article is protected by copyright. All rights reserved.]

Published
2023

3. Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA‐MeDALL hypothesis

Author

Bousquet, J., primary, Melén, E., additional, Haahtela, T., additional, Koppelman, G. H., additional, Togias, A., additional, Valenta, R., additional, Akdis, C. A., additional, Czarlewski, W., additional, Rothenberg, M., additional, Valiulis, A., additional, Wickman, M., additional, Akdis, M., additional, Aguilar, D., additional, Bedbrook, A., additional, Bindslev‐Jensen, C., additional, Bosnic‐Anticevich, S., additional, Boulet, L. P., additional, Brightling, C. E., additional, Brussino, L., additional, Burte, E., additional, Bustamante, M., additional, Canonica, G. W., additional, Cecchi, L., additional, Celedon, J. C., additional, Chaves Loureiro, C., additional, Costa, E., additional, Cruz, A. A., additional, Erhola, M., additional, Gemicioglu, B., additional, Fokkens, W. J., additional, Garcia‐Aymerich, J., additional, Guerra, S., additional, Heinrich, J., additional, Ivancevich, J. C., additional, Keil, T., additional, Klimek, L., additional, Kuna, P., additional, Kupczyk, M., additional, Kvedariene, V., additional, Larenas‐Linnemann, D. E., additional, Lemonnier, N., additional, Lodrup Carlsen, K. C., additional, Louis, R., additional, Makela, M., additional, Makris, M., additional, Maurer, M., additional, Momas, I., additional, Morais‐Almeida, M., additional, Mullol, J., additional, Naclerio, R. N., additional, Nadeau, K., additional, Nadif, R., additional, Niedoszytko, M., additional, Okamoto, Y., additional, Ollert, M., additional, Papadopoulos, N. G., additional, Passalacqua, G., additional, Patella, V., additional, Pawankar, R., additional, Pham‐Thi, N., additional, Pfaar, O., additional, Regateiro, F. S., additional, Ring, J., additional, Rouadi, P. W., additional, Samolinski, B., additional, Sastre, J., additional, Savouré, M., additional, Scichilone, N., additional, Shamji, M. H., additional, Sheikh, A., additional, Siroux, V., additional, Sousa‐Pinto, B., additional, Standl, M., additional, Sunyer, J., additional, Taborda‐Barata, L., additional, Toppila‐Salmi, S., additional, Torres, M. J., additional, Tsiligianni, I., additional, Valovirta, E., additional, Vandenplas, O., additional, Ventura, M. T., additional, Weiss, S., additional, Yorgancioglu, A., additional, Zhang, L., additional, Abdul Latiff, A. H., additional, Aberer, W., additional, Agache, I., additional, Al‐Ahmad, M., additional, Alobid, I., additional, Ansotegui, I. J., additional, Arshad, S. H., additional, Asayag, E., additional, Barbara, C., additional, Baharudin, A., additional, Battur, L., additional, Bennoor, K. S., additional, Berghea, E. C., additional, Bergmann, K. C., additional, Bernstein, D., additional, Bewick, M., additional, Blain, H., additional, Bonini, M., additional, Braido, F., additional, Buhl, R., additional, Bumbacea, R. S., additional, Bush, A., additional, Calderon, M., additional, Calvo‐Gil, M., additional, Camargos, P., additional, Caraballo, L., additional, Cardona, V., additional, Carr, W., additional, Carreiro‐Martins, P., additional, Casale, T., additional, Cepeda Sarabia, A. M., additional, Chandrasekharan, R., additional, Charpin, D., additional, Chen, Y. Z., additional, Cherrez‐Ojeda, I., additional, Chivato, T., additional, Chkhartishvili, E., additional, Christoff, G., additional, Chu, D. K., additional, Cingi, C., additional, Correia de Sousa, J., additional, Corrigan, C., additional, Custovic, A., additional, D’Amato, G., additional, Del Giacco, S., additional, De Blay, F., additional, Devillier, P., additional, Didier, A., additional, do Ceu Teixeira, M., additional, Dokic, D., additional, Douagui, H., additional, Doulaptsi, M., additional, Durham, S., additional, Dykewicz, M., additional, Eiwegger, T., additional, El‐Sayed, Z. A., additional, Emuzyte, R., additional, Fiocchi, A., additional, Fyhrquist, N., additional, Gomez, R. M., additional, Gotua, M., additional, Guzman, M. A., additional, Hagemann, J., additional, Hamamah, S., additional, Halken, S., additional, Halpin, D. M. G., additional, Hofmann, M., additional, Hossny, E., additional, Hrubiško, M., additional, Irani, C., additional, Ispayeva, Z., additional, Jares, E., additional, Jartti, T., additional, Jassem, E., additional, Julge, K., additional, Just, J., additional, Jutel, M., additional, Kaidashev, I., additional, Kalayci, O., additional, Kalyoncu, A. F., additional, Kardas, P., additional, Kirenga, B., additional, Kraxner, H., additional, Kull, I., additional, Kulus, M., additional, La Grutta, S., additional, Lau, S., additional, Le Tuyet Thi, L., additional, Levin, M., additional, Lipworth, B., additional, Lourenço, O., additional, Mahboub, B., additional, Martinez‐Infante, E., additional, Matricardi, P., additional, Miculinic, N., additional, Migueres, N., additional, Mihaltan, F., additional, Mohammad, Y., additional, Moniuszko, M., additional, Montefort, S., additional, Neffen, H., additional, Nekam, K., additional, Nunes, E., additional, Nyembue Tshipukane, D., additional, O’Hehir, R., additional, Ogulur, I., additional, Ohta, K., additional, Okubo, K., additional, Ouedraogo, S., additional, Olze, H., additional, Pali‐Schöll, I., additional, Palomares, O., additional, Palosuo, K., additional, Panaitescu, C., additional, Panzner, P., additional, Park, H. S., additional, Pitsios, C., additional, Plavec, D., additional, Popov, T. A., additional, Puggioni, F., additional, Quirce, S., additional, Recto, M., additional, Repka‐Ramirez, M. S., additional, Robalo Cordeiro, C., additional, Roche, N., additional, Rodriguez‐Gonzalez, M., additional, Romantowski, J., additional, Rosario Filho, N., additional, Rottem, M., additional, Sagara, H., additional, Serpa, F. S., additional, Sayah, Z., additional, Scheire, S., additional, Schmid‐Grendelmeier, P., additional, Sisul, J. C., additional, Sole, D., additional, Soto‐Martinez, M., additional, Sova, M., additional, Sperl, A., additional, Spranger, O., additional, Stelmach, R., additional, Suppli Ulrik, C., additional, Thomas, M., additional, To, T., additional, Todo‐Bom, A., additional, Tomazic, P. V., additional, Urrutia‐Pereira, M., additional, Valentin‐Rostan, M., additional, Van Ganse, E., additional, van Hage, M., additional, Vasankari, T., additional, Vichyanond, P., additional, Viegi, G., additional, Wallace, D., additional, Wang, D. Y., additional, Williams, S., additional, Worm, M., additional, Yiallouros, P., additional, Yusuf, O., additional, Zaitoun, F., additional, Zernotti, M., additional, Zidarn, M., additional, Zuberbier, J., additional, Fonseca, J. A., additional, Zuberbier, T., additional, and Anto, J. M., additional

Published
2023
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4. The ARIA-MeDALL hypothesis

Author

Bousquet, J, Melén, E, Haahtela, T, Koppelman, G H, Togias, A, Valenta, R, Akdis, C A, Czarlewski, W, Rothenberg, M, Valiulis, A, Wickmann, M, Bonini, M, Braido, F, Buhl, R, Bumbacea, R, Bush, A, Calderon, M, Calvo, G, Camargos, P, Caraballo, L, Cardona, V, Aguilar, D, Carr, W, Carreiro-Martins, P, Casale, T, Cepeda Sarabia, A M, Chandrasekharan, R, Charpin, D, Chen, Y Z, Cherrez-Ojeda, I, Chivato, T, Chkhartishvili, E, Akdis, M, Christoff, G, Chu, D K, Cingi, C, Correia da Sousa, J, Corrigan, C, Custovic, A, D'Amato, G, Del Giacco, S, De Blay, F, Devillier, P, Ansotegui, I J, Didier, A, do Ceu Teixeira, M, Dokic, D, Douagui, H, Doulaptsi, M, Durham, S, Dykewicz, M, Eiwegger, T, El-Sayed, Z A, Emuzyte, R, Barbara, C, Fiocchi, A, Fyhrquist, N, Gomez, R M, Gotua, M, Guzman, M A, Hagemann, J, Hamamah, S, Halken, S, Halpin, D M G, Bedbrook, A, Hofmann, M, Hossny, E, Hrubiško, M, Irani, C, Ispayeva, Z, Jares, E, Jartti, T, Jassem, E, Julge, K, Just, J, Bindslev Jensen, C, Jutel, M, Kaidashev, I, Kalayci, O, Kalyoncu, O, Kardas, P, Kirenga, B, Kraxner, H, Kull, I, Kulus, M, La Gruta, S, Bosnic-Anticevich, S, Lau, S, Le Tuyet Thi, L, Levin, M, Lipworth, B, Lourenço, O, Mahboub, B, Mäkelä, M J, Martinez-Infante, E, Matricardi, P, Miculinic, N, Boulet, L P, Migueres, N, Mihaltan, F, Mohamad, Y, Moniusko, M, Montefort, S, Neffen, H, Nekam, K, Nunes, E, Nyembue Tshipukane, D, O'Hehir, R E, Brightling, C E, Ogulur, I, Ohta, K, Okubo, K, Ouedraogo, S, Olze, H, Pali-Schöll, I, Palomares, O, Palosuo, K, Panaitescu, C, Panzner, P, Brussino, L, Park, H S, Pitsios, C, Plavec, D, Popov, T A, Puggioni, F, Quirce, S, Recto, M, Repka-Ramirez, R, Roballo-Cordeiro, C, Roche, N, Burte, E, Rodriguez-Gonzales, M, Romantowski, J, Rosario Filho, N, Rottem, M, Sagara, H, Sarquis-Serpa, F, Sayah, Z, Scheire, S, Schmid-Grendelmeier, P, Sisul, J C, Bustamante, M, Sole, D, Soto-Martinez, M, Sova, M, Sperl, A, Spranger, O, Stelmach, R, Suppli Ulrik, C, Thomas, M, To, T, Todo-Bom, A, Canonica, G W, Tomazic, P V, Urrutia-Pereira, M, Valentin-Rostan, M, van Ganse, E, Van Hage, M, Vasankari, T, Vichyanond, P, Viegi, G, Wallace, D, Wang, D Y, Cecchi, L, Williams, S, Worm, M, Yiallouros, P, Yusuf, O, Zaitoun, F, Zernotti, M, Zidarn, M, Zuberbier, J, Fonseca, J A, Celedon, J C, Zuberbier, T, Anto, J M, Chaves-Loureiro, C, Costa, E, Cruz, A A, Erhola, M, Gemicioglu, B, Fokkens, W J, Garcia Aymerich, J, Guerra, S, Heinrich, J, Ivancevich, J C, Keil, T, Klimek, L, Kuna, P, Kupczyk, M, Kvedariene, V, Larenas-Linnemann, D E, Lemonnier, N, Lodrup Carlsen, K C, Louis, R, Makris, M, Maurer, M, Momas, I, Morais-Almeida, M, Mullol, J, Naclerio, R N, Nadeau, K, Nadif, R, Niedoszytko, M, Okamoto, Y, Ollert, M, Papadopoulos, N G, Passalacqua, G, Patella, V, Pawankar, R, Pham-Thi, N, Pfaar, O, Regateiro, F S, Ring, J, Rouadi, P W, Samolinski, B, Sastre, J, Savouré, M, Scichilone, N, Shamji, M H, Sheikh, A, Siroux, V, Sousa-Pinto, B, Standl, M, Sunyer, J, Taborda-Barata, L, Toppila-Salmi, S, Torres, M J, Tsiligianni, I, Valovirta, E, Vandenplas, O, Ventura, M T, Weiss, S, Yorgancioglu, A, Zhang, L, Abdul Latiff, A H, Aberer, W, Agache, I, Al-Ahmad, M, Alobid, I, Arshad, H S, Asayag, E, Baharudin, A, Battur, L, Bennoor, K S, Berghea, E C, Bergmann, K C, Bernstein, D, Bewick, M, Blain, H, UCIBIO - Applied Molecular Biosciences Unit, Comprehensive Health Research Centre (CHRC) - pólo NMS, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
SDG 3 - Good Health and Well-being
Abstract

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. authorsversion epub_ahead_of_print

Published
2023

5. ALLERGIC SENSITIZATION AND CLINICAL CHARACTERISTICS OF CHILDREN WITH OCULAR ALLERGY

Author

Neto, H. Chong, Marino, L., Wandalsen, G., Rosario-Filho, N., and Rosario, C.

Abstract

Ocular allergy is an important, but underdiagnosed and undertreated disease which negatively affects quality of life. The main objective of this study is to describe the symptoms, severity of OA and the allergic sensitization profile of children treated at the Allergy and Immunology service at CHC-UFPR.

Published
2024
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6. A WAO - ARIA - GA2LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020

Author

Ansotegui, IJ, Melioli, G, Canonica, GW, Maximiliano Gomez, R, Jensen-Jarolim, E, Ebisawa, M, Luengo, O, Caraballo, L, Passalacqua, G, Poulsen, LK, Savi, E, Zuberbier, T, Villa, E, Oppenheimer, J, Asero, R, Bernstein, J, Bousquet, J, Cardona, V, Cox, L, Demoly, P, Ferreira, F, Bianchi, PG, Gonzalez Diaz, S, Jakob, T, Tanno, LK, Kleine-Tebbe, J, Levin, M, Martin, B, Matricardi, PM, Monge Ortega, OP, Almeida, MM, Nunes, C, Ortega Martell, JA, Renz, H, Rosario Filho, N, Rouadi, P, Ruiba, A, Sampson, H, Sanchez Borges, M, Scala, E, Schmid-Grendelmeier, P, Senna, G-E, Carlos Sisul, J, Tang, MLK, Valenta, R, van Hage, M, Wong, GWK, Yanez, A, Ansotegui, IJ, Melioli, G, Canonica, GW, Maximiliano Gomez, R, Jensen-Jarolim, E, Ebisawa, M, Luengo, O, Caraballo, L, Passalacqua, G, Poulsen, LK, Savi, E, Zuberbier, T, Villa, E, Oppenheimer, J, Asero, R, Bernstein, J, Bousquet, J, Cardona, V, Cox, L, Demoly, P, Ferreira, F, Bianchi, PG, Gonzalez Diaz, S, Jakob, T, Tanno, LK, Kleine-Tebbe, J, Levin, M, Martin, B, Matricardi, PM, Monge Ortega, OP, Almeida, MM, Nunes, C, Ortega Martell, JA, Renz, H, Rosario Filho, N, Rouadi, P, Ruiba, A, Sampson, H, Sanchez Borges, M, Scala, E, Schmid-Grendelmeier, P, Senna, G-E, Carlos Sisul, J, Tang, MLK, Valenta, R, van Hage, M, Wong, GWK, and Yanez, A

Abstract

Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@. PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies.

Published
2020

7. Selective IgM deficiency: evaluation of 75 patients according to different diagnostic criteria.

Author

Batista CHR, Smanio MCM, Poltronieri PB, Resende LL, Kokron CM, Barros MT, Agondi RC, Ferraroni NR, Roxo-Junior P, Ferriani MPL, Chong-Neto H, Rosario Filho N, Kamoi TO, Di Gesu R, Goudouris E, Aranda CS, Mansour E, Henriques MT, Bardou MLD, Antila HG, and Grumach AS

Subjects
Humans, Female, Male, Retrospective Studies, Middle Aged, Adult, Aged, Child, Adolescent, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes immunology, Immunoglobulin M blood
Abstract

Selective IgM deficiency (SIgMD) has recently been included in the inborn errors of immunity classification. SIgMD has conflicting diagnostic criteria and diverse clinical and immunological findings. We aimed to assess the clinical and laboratory profiles of patients with SIgMD and to compare the data of patients diagnosed using two inclusion criteria. This was a descriptive, retrospective, observational, collaborative study. Patients were included according to the following definitions: Group 1, IgM levels < 0.20 g/L in children and < 0.30 g/L in adults, and Group 2, serum IgM levels below 2SD and, for both, absence of associated immunological diseases or secondary causes. The protocol was approved by the Ethics Committee, and patients provided consent. In total, 75 patients were included: 37 (16 M:21F; mean age, 52.92) and 38 (13 M:25F; mean age, 53.47) in Groups 1 and 2, respectively. The most frequent clinical manifestations were allergic rhinitis (G1, 45.9%; G2, 36.8%), asthma (G1, 37.8%; G2, 28.9%), and pulmonary infections (G1, 27.03%; G2, 21.05%). Chromosomopathies (16.22%) and neoplasia (13.51%) were more frequent in G1, whereas URTI (23.68%) and skin infections (23.68%) were more common in G2. There was no difference in sex or mean age at symptom onset between both groups of patients. Regarding the clinical picture, 90.7% of the lesions were benign (68/75). Chromosomopathies may be associated with SIgMD, suggesting the need to quantify serum IgM levels in these cases. Considering the possibility of developing autoimmunity, neoplasia, and common variable immunodeficiency, it is advisable to follow up patients with SIgMD., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University Center FMABC on January 17, 2021 (CAAE 52536915.5.0000.0082). All the authors were consulted and consented to participate and submit to the Journal of Clinical Immunology. Consent to participate: Informed consent was obtained from all individual participants included in the study. The consent was read and explained for each participant, and all the text was previously revised by the ethical committee. Patients younger than 18 years old had a specific consent, and the parent or legal guardian also signed the consent to participate in the study. Consent for publication: The patient or in the case of patients less than 18 years old, his/her parent or legal guardian authorized the publication of the results without identifying their names. The patients were nominated by numbers to maintain their identity anonymous. Conflict of interest: No conflicts of interest related to this project. ASG belongs to the editorial board. ASG has been a consultant and/or speaker for CSL Behring, Takeda, and Catalyst. CMK has been a speaker for Takeda. PRJ has been a consultant and/or speaker for CSL Behring, Takeda, Novartis, and Sanofi. EM has been a speaker for Takeda, CSL Behring, Novartis, and Sanofi and a consultant for Takeda and CSL Behring. CSA has been a speaker for Takeda, CSL Behring, Sanofi, and Roche and a consultant for PTC, EUSA Pharma, and Sanofi., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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8. Why fexofenadine is considered as a truly non-sedating antihistamine with no brain penetration: a systematic review.

Author

Ansotegui IJ, Bousquet J, Canonica GW, Demoly P, Gómez RM, Meltzer EO, Murrieta-Aguttes M, Naclerio RM, Rosario Filho N, and Scadding GK

Subjects
Humans, Brain drug effects, Brain diagnostic imaging, Brain metabolism, Blood-Brain Barrier metabolism, Blood-Brain Barrier drug effects, Rhinitis, Allergic drug therapy, Urticaria drug therapy, Terfenadine analogs & derivatives, Terfenadine pharmacokinetics, Terfenadine pharmacology, Terfenadine administration & dosage, Histamine H1 Antagonists, Non-Sedating pharmacokinetics, Histamine H1 Antagonists, Non-Sedating administration & dosage, Histamine H1 Antagonists, Non-Sedating pharmacology, Histamine H1 Antagonists, Non-Sedating adverse effects
Abstract

Objective: Fexofenadine is a second-generation inverse agonist of H 1 -receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria., Methods: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo., Results: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H 1 -receptor occupancy (H 1 RO) obtained from PET showed no H 1 RO by fexofenadine, the receptor which is known to cause sedation of H 1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses., Conclusion: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.

Published
2024
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9. Pregnancy in Patients With Hereditary Angioedema and Normal C1 Inhibitor.

Author

Gabriel N, Marcelino F, Ferriani MPL, Arruda LK, Campos RA, Gonçalves RF, Chong-Neto H, Rosario Filho N, Valle SOR, Pesquero JB, and Grumach AS

Abstract

Background: HAE with normal C1 inhibitor (HAE-nC1-INH) has been identified as a bradykinin mediated angioedema. Estrogens are one of the main trigger factors. Pregnancy in HAE with C1 inhibitor deficiency showed variable course, however, few reports are available for HAE-nC1-INH. We evaluated the course of pregnancies in women diagnosed with HAE-nC1-INH., Methods: Women with diagnosis of HAE-nC1-INH according to the following criteria: clinical manifestations similar to HAE-C1-INH, normal biochemical evaluation and family history were included. A questionnaire about pregnancies was applied after consent. Genetic evaluation for known mutations was performed in all patients., Results: A total of 45 pregnancies occurring in 26 HAE-nC1-INH patients were evaluated (7/26 patients with F12 variant). Spontaneous abortion was reported in 8/45 (17.8%) pregnancies. Onset of attacks started before the pregnancy in 18/26 patients; during the pregnancy in 2/26; and after the pregnancy in 6/26. HAE attacks occurred in 24/37 pregnancies (64,7%): during the 1st trimester in 41.7%; 2nd trimester in 12.5%; 3rd trimester in 20.8%; 1st and 3rd trimesters in 4.2% and during the whole pregnancy in 20.8%. Among 15/18 patients who had attacks before pregnancy, symptoms persisted with worsening in 9/15; improvement in 4/15; no change in 1/15, and no response in 1/15., Conclusions: The occurrence of abortion in HAE-nC1-INH was similar to the expected for not affected women. The 1st trimester of the pregnancy was more symptomatic for HAE-nC1-INH women. Considering the strong relevance of estrogens in HAE-nC1-INH, pregnancy could worsen the course of disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gabriel, Marcelino, Ferriani, Arruda, Campos, Gonçalves, Chong-Neto, Rosario Filho, Valle, Pesquero and Grumach.)

Published
2022
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10. The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil.

Author

Arruda E, Jones MH, Escremim de Paula F, Chong D, Bugarin G, Notario G, Matsuno AK, Pitrez PM, Vo P, Suzuki C, Rosario Filho N, and Stein RT

Subjects
Brazil epidemiology, Coinfection virology, Epidemiologic Studies, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Prospective Studies, Viruses classification, Coinfection epidemiology, Infant, Premature, Respiratory Syncytial Virus Infections complications, Respiratory Syncytial Virus Infections epidemiology, Respiratory Tract Infections epidemiology, Viruses isolation & purification
Abstract

Background: Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes., Methods: This prospective epidemiologic study of severe LRTI incidence among children born ≤35 weeks gestational age at 3 sites in Brazil (2008-2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI., Results: Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05)., Conclusions: This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

Published
2014
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11. Fluticasone/formoterol dry powder versus budesonide/formoterol in adults and adolescents with uncontrolled or partly controlled asthma.

Author

Cukier A, Jacob CM, Rosario Filho NA, Fiterman J, Vianna EO, Hetzel JL, Neis MA, Fiss E, Castro FF, Fernandes AL, Stirbulov R, and Pizzichini E

Subjects
Administration, Inhalation, Adolescent, Adult, Aged, Androstadienes administration & dosage, Androstadienes adverse effects, Anti-Asthmatic Agents adverse effects, Asthma physiopathology, Budesonide administration & dosage, Budesonide adverse effects, Child, Drug Combinations, Dry Powder Inhalers, Ethanolamines administration & dosage, Ethanolamines adverse effects, Female, Fluticasone, Forced Expiratory Volume drug effects, Formoterol Fumarate, Humans, Male, Middle Aged, Peak Expiratory Flow Rate drug effects, Treatment Outcome, Young Adult, Anti-Asthmatic Agents administration & dosage, Asthma prevention & control
Abstract

Unlabelled: This 12-week study compared the efficacy and safety of a fixed combination of fluticasone propionate plus formoterol (FL/F) 250/12 μg b.i.d. administered via a dry powder inhaler (DPI) (Libbs Farmacêutica, Brazil) to a combination of budesonide plus formoterol (BD/F) 400/12 μg b.i.d. After a 2-week run-in period (in which all patients were treated exclusively with budesonide plus formoterol), patients aged 12-65 years of age (N = 196) with uncontrolled asthma were randomized into an actively-controlled, open-labeled, parallel-group, multicentre, phase III study. The primary objective was to demonstrate non-inferiority, measured by morning peak expiratory flow (mPEF). The non-inferiority was demonstrated. A statistically significant improvement from baseline was observed in both groups in terms of lung function, asthma control, and the use of rescue medication. FL/F demonstrated a statistical superiority to BD/F in terms of lung function (FEV(1)) (p = 0.01) and for asthma control (p = 0.02). Non-significant between-group differences were observed with regards to exacerbation rates and adverse events. In uncontrolled or partly controlled asthma patients, the use of a combination of fluticasone propionate plus formoterol via DPI for 12-weeks was non-inferior and showed improvements in FEV(1) and asthma control when compared to a combination of budesonide plus formoterol. (, Clinical Trial Number: ISRCTN60408425)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Published
2013
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12. Anaphylaxis associated with the vaccine against measles, mumps and rubella.

Author

Novadzki IM and Rosario Filho N

Subjects
Anaphylaxis immunology, Case-Control Studies, Child, Preschool, Dextrans immunology, Female, Humans, Immunoglobulin E immunology, Male, Measles-Mumps-Rubella Vaccine immunology, Skin Tests, Anaphylaxis etiology, Measles-Mumps-Rubella Vaccine adverse effects
Abstract

A case-control study was carried out aiming to describe the cases and causes of anaphylaxis associated with the vaccine against measles, mumps and rubella. A total of 22 reported cases in children who showed mucocutaneous manifestations, during the Campanha Nacional de Vacinação (Brazilian Vaccination Campaign), conducted in the city of Curitiba, Southern Brazil, in 2004, were studied. In addition, 66 children, who were next to these cases and did not show a symptomatology after the vaccine was applied, were selected. Serum measurements of antibodies for vaccine antigens and total IgE, specific IgE antibody measurements for several allergens, and skin tests were performed. Vaccine response was adequate, specific IgE measurement and skin tests showed that potential allergens in vaccines and atopy were not associated with anaphylactic reactions. Skin tests with the vaccine and dextran were positive in the cases exclusively, suggesting sensitization to certain residual components of the vaccine and possible cross-reaction with dextran.

Published
2010
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13. The International Study of Wheezing in Infants: questionnaire validation.

Author

Mallol J, García-Marcos L, Aguirre V, Martinez-Torres A, Perez-Fernández V, Gallardo A, Calvo M, Rosario Filho N, Rocha W, Fischer G, Baeza-Bacab M, Chiarella P, Pinto R, and Barria C

Subjects
Case-Control Studies, Cross-Sectional Studies, Humans, Infant, Latin America, Parents, Physicians, Prevalence, Recurrence, Spain, Respiratory Sounds diagnosis, Respiratory Sounds immunology, Surveys and Questionnaires
Abstract

Background: There are no internationally validated questionnaires to investigate the prevalence of infant wheezing. This study was undertaken to validate a questionnaire for the International Study on the Prevalence of Wheezing in Infants (Estudio Internacional de Sibilancias en Lactantes, EISL)., Material and Methods: Construct and criterion validity were tested for the question 'Has your baby had wheezing or whistling in the chest during his/her first 12 months of life?'. Construct validity (i.e. the ability of parents and doctors to refer to the same symptoms with the same words) was tested in a sample of 50 wheezing and 50 non-wheezy infants 12-15 months of age in each of 10 centres from 6 different Spanish- or Portuguese-speaking countries. Criterion validity (i.e. the ability of parents to correctly detect the symptom in the general population) was evaluated in 2 samples (Santiago, Chile and Cartagena, Spain) of 50 wheezing and 50 non-wheezing infants (according to parents) of the same age, randomly selected from the general population, who were later blindly diagnosed by a paediatric pulmonologist., Results: Construct validity was very high (kappa test: 0.98-1) in all centres. According to Youden's index, criterion validity was good both in Cartagena (75.5%) and in Santiago (67.0%). Adding questions about asthma medication did not improve diagnosis accuracy., Conclusions: The EISL questionnaire significantly distinguished wheezy infants from healthy ones. This questionnaire has a strong validity and can be employed in large international multicentre studies on wheezing during infancy.

Published
2007
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