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1. Population pharmacokinetics of levocetirizine in very young children: the pediatricians' perspective

Author: Simons FE, ETAC study group, MASI, MASSIMO, SPECCHIA, FERNANDO GIUSEPPE, Simons FE, Masi M, Specchia F, and ETAC study group
Subjects: Histamine H1 Antagonists, Non-Sedating, medicine.medical_specialty, Allergy, Immunology, Population, Administration, Oral, Pharmacology, Pediatrics, Piperazines, Levocetirizine, Dermatitis, Atopic, Pharmacokinetics, Physicians, Internal medicine, medicine, Humans, Immunology and Allergy, Ingestion, Dosing, education, Volume of distribution, education.field_of_study, Models, Statistical, business.industry, Infant, medicine.disease, Cetirizine, Child, Preschool, Pediatrics, Perinatology and Child Health, business, medicine.drug
Abstract: Developmental changes during infancy and childhood can affect drug pharmacokinetics (PK), i.e., absorption, distribution, metabolism, and renal excretion. This, in turn, influences optimal dosing, efficacy, and safety. To date, of the 40 H1-antihistamines available worldwide, only 11 have been studied in children using a PK approach. Here, we provide the pediatricians' perspective on the population PK of levocetirizine, the pharmacologically active enantiomer of cetirizine, in very young children who received oral cetirizine, and describe the factors that influence levocetirizine PK in this population. In a prospective, randomized, double-blind, parallel-group, placebo-controlled study, very young children received oral cetirizine 0.25 mg/kg twice daily for 18 months. Plasma levocetirizine concentrations were measured in timed, sparse blood samples collected at steady-state (3, 12 and 18 months after commencement of treatment) for the purpose of monitoring safety, and levocetirizine population, PK parameters were derived by using non-linear mixed effects modeling. In 343 children (age 14-46 months, body weight 8.2-20.5 kg), a total of 943 blood samples were obtained. Compliance with cetirizine dosing was documented. The population PK model used predicted that with increasing body weight, levocetirizine oral clearance would increase by 0.044 l/h/kg, and levocetirizine volume of distribution would increase by 0.639 l/kg. Levocetirizine PK were not influenced by eosinophilia, sensitization to allergens, allergic disease, gastroenteritis/diarrhea, or concomitant ingestion of other medications. This population PK model predicts that in very young children, the oral clearance of levocetirizine will be rapid and will increase as body weight and age increase, therefore, levocetirizine dosing should be based on body weight and age in this population. Compared with older patients, on a mg/kg basis, relatively higher doses may be needed, and twice-daily dosing may be necessary, as previously reported for the related racemic H1-antihistamine cetirizine.
Published: 2005

2. Development and implementation of guidelines in allergic rhinitis - an ARIA-GA2LEN paper

Author: Bousquet, J, Schünemann, Hj, Zuberbier, T, Bachert, C, Baena Cagnani CE, Bousquet, Pj, Brozek, J, Canonica, Giorgio, Casale, Tb, Demoly, P, Gerth van Wijk, R, Ohta, K, Bateman, Ed, Calderon, M, Cruz, Aa, Dolen, Wk, Haughney, J, Lockey, Rf, Lötvall, J, O'Byrne, P, Spranger, O, Togias, A, Bonini, S, Boulet, Lp, Camargos, P, Carlsen, Kh, Chavannes, Nh, Delgado, L, Durham, Sr, Fokkens, Wj, Fonseca, J, Haahtela, T, Kalayci, O, Kowalski, Ml, Larenas Linnemann, D, Li, J, Mohammad, Y, Mullol, J, Naclerio, R, O'Hehir, Re, Papadopoulos, N, Passalacqua, G, Rabe, Kf, Pawankar, R, Ryan, D, Samolinski, B, Simons, Fe, Valovirta, E, Yorgancioglu, A, Yusuf, Om, Agache, I, Aït Khaled, N, Annesi Maesano, I, Beghe, B, Ben Kheder, A, Blaiss, Ms, Boakye, Da, Bouchard, J, Burney, Pg, Busse, Ww, Chan Yeung, M, Chen, Y, Chuchalin, Ag, Costa, Dj, Custovic, A, Dahl, R, Denburg, J, Douagui, H, Emuzyte, R, Grouse, L, Humbert, M, Jackson, C, Johnston, Sl, Kaliner, Ma, Keith, Pk, Kim, Yy, Klossek, Jm, Kuna, P, Le, Lt, Lemiere, C, Lipworth, B, Mahboub, B, Malo, Jl, Marshall, Gd, Mavale Manuel, S, Meltzer, Eo, Morais Almeida, M, Motala, C, Naspitz, C, Nekam, K, Niggemann, B, Nizankowska Mogilnicka, E, Okamoto, Y, Orru, Mp, Ouedraogo, S, Palkonen, S, Popov, Ta, Price, D, Rosado Pinto, J, Scadding, Gk, Sooronbaev, Tm, Stoloff, Sw, Toskala, E, van Cauwenberge, P, Vandenplas, O, van Weel, C, Viegi, G, Virchow, Jc, Wang, Dy, Wickman, M, Williams, D, Yawn, Bp, Zar, Hj, Zernotti, M, Zhong, N, In collaboration with the WHO Collaborating Center of Asthma, Rhinitis, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Photochimie moléculaire et macromoléculaire (PMM), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), P&A Kyriakou Children's Hospital, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), inconnu, Inconnu, Forschungszentrum Jülich GmbH - Projektträger BEO, GmbH, Laboratoire d'étude des textures et application aux matériaux (LETAM), Université Paul Verlaine - Metz (UPVM)-Centre National de la Recherche Scientifique (CNRS), Merlin Circuit Technology LTD, Institute for Meteorology and Climate Research (IMK), Karlsruhe Institute of Technology (KIT), Physics Department [UNB], University of New Brunswick (UNB), Bousquet J, Schünemann HJ, R Gerth van Wijk, K Ohta, Bateman ED, M Calderon, Cruz AA, Dolen WK, Haughney J, Lockey RF, Lötvall J, P O'Byrne, Zuberbier T, O Spranger, Togias A, S Bonini, LP Boulet, P Camargos, KH Carlsen, Chavannes NH, L Delgado, SR Durham, Fokkens WJ, C Bachert, Fonseca J, Haahtela T, O Kalayci, ML Kowalski, Larenas-Linnemann D, Li J, Y Mohammad, Mullol J, R Naclerio, RE O'Hehir, Baena-Cagnani CE, N Papadopoulos, G Passalacqua, KF Rabe, R Pawankar, Ryan D, B Samolinski, Simons FE, E Valovirta, Yorgancioglu A, Yusuf OM, Bousquet PJ, je Agache, Khaled N-Aït, Annesi-Maesano I, B Begge, Kheder Ben A, MS Blaiss, DA Boakye, Bouchard J, PG Burney, WW Busse, Brozek J, M Chan-Yeung, Y Chen, AG Chuchalin, Costa DJ, Custovic A, R Dahl, Denburg J, H Douagui, R Emuzyte, L Grouse, GW Canonica, M Humbert, C Jackson, SL Johnston, MA Kaliner, Keith PK, YY Kim, JM Klossek, P Kun, la tuberculose Casale, Demoly P, AII - Amsterdam institute for Infection and Immunity, Ear, Nose and Throat, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, Centre National de la Recherche Scientifique (CNRS)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut de Chimie du CNRS (INC), and Internal Medicine
Subjects: Evidence-Based Medicine, Rhinitis, Allergic, Perennial, MESH: Humans, treatment, MESH: Asthma, MESH: Rhinitis, Allergic, Perennial, rhinitis, asthma, guidelines, Disease Management, Rhinitis, Allergic, Seasonal, MESH: Rhinitis, Allergic, Seasonal, Planning Techniques, MESH: Planning Techniques, MESH: Disease Management, Asthma, MESH: Practice Guidelines as Topic, Practice Guidelines as Topic, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ARIA asthma EAACI EFA GA2LEN IPCRG rhinitis nonallergic rhinitis controlled-trial severe asthma randomized-trials consort statement primary-care 2008 update recommendations management quality, MESH: Evidence-Based Medicine
Abstract: International audience; The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.
Published: 2010

3. The allergic sensitization in infants with atopic eczema from different countries

Author: DE BENEDICTIS FM, FRANCESCHINI F, HILL D, NASPITZ C, SIMONS FE, WAHN U, WARNER JO, DE LONGUEVILLE M, DECIMO, Fabio, CAPRISTO, Carlo, MIRAGLIA DEL GIUDICE, Michele, DE BENEDICTIS, Fm, Franceschini, F, Hill, D, Naspitz, C, Simons, Fe, Wahn, U, Warner, Jo, DE LONGUEVILLE, M, Decimo, Fabio, Capristo, Carlo, and MIRAGLIA DEL GIUDICE, Michele
Published: 2009

4. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Author: Bousquet, J, Khaltaev, N, Cruz, Aa, Denburg, J, Fokkens, Wj, Togias, A, Zuberbier, T, Baena Cagnani CE, Canonica, Giorgio, van Weel, C, Agache, I, Aït Khaled, N, Bachert, C, Blaiss, Ms, Bonini, S, Boulet, Lp, Bousquet, Pj, Camargos, P, Carlsen, Kh, Chen, Y, Custovic, A, Dahl, R, Demoly, P, Douagui, H, Durham, Sr, van Wijk RG, Kalayci, O, Kaliner, Ma, Kim, Yy, Kowalski, Ml, Kuna, P, Le, Lt, Lemiere, C, Li, J, Lockey, Rf, Mavale Manuel, S, Meltzer, Eo, Mohammad, Y, Mullol, J, Naclerio, R, O'Hehir, Re, Ohta, K, Ouedraogo, S, Palkonen, S, Papadopoulos, N, Passalacqua, Giovanni, Pawankar, R, Popov, Ta, Rabe, Kf, Rosado Pinto, J, Scadding, Gk, Simons, Fe, Toskala, E, Valovirta, E, van Cauwenberge, P, Wang, Dy, Wickman, M, Yawn, Bp, Yorgancioglu, A, Yusuf, Om, Zar, H, Annesi Maesano, I, Bateman, Ed, Ben Kheder, A, Boakye, Da, Bouchard, J, Burney, P, Busse, Ww, Chan Yeung, M, Chavannes, Nh, Chuchalin, A, Dolen, Wk, Emuzyte, R, Grouse, L, Humbert, M, Jackson, C, Johnston, Sl, Keith, Pk, Kemp, Jp, Klossek, Jm, Larenas Linnemann, D, Lipworth, B, Malo, Jl, Marshall, Gd, Naspitz, C, Nekam, K, Niggemann, B, Nizankowska Mogilnicka, E, Okamoto, Y, Orru, Mp, Potter, P, Price, D, Stoloff, Sw, Vandenplas, O, Viegi, G, Williams, D, World Health Organization, Galen, Allergen, Bousquet, J, Khaltaev, N, Cruz, Aa, Denburg, J, Fokkens, Wj, Togias, A, Zuberbier, T, BAENA CAGNANI, Ce, Canonica, Gw, VAN WEEL, C, Agache, I, AÏT KHALED, N, Bachert, C, Blaiss, M, Bonini, Sergio, Boulet, Lp, Bousquet, Pj, Camargos, P, Carlsen, Kh, Chen, Y, Custovic, A, Dahl, R, Demoly, P, Douagui, H, Durham, Sr, VAN WIJK, Rg, Kalayci, O, Kaliner, Ma, Kim, Yy, Kowalski, Ml, Kuna, P, Le, Lt, Lemiere, C, Li, J, Lockey, Rf, MAVALE MANUEL, S, Meltzer, Eo, Mohammad, Y, Mullol, J, Naclerio, R, O'Hehir, Re, Ohta, K, Ouedraogo, S, Palkonen, S, Papadopoulos, N, Passalacqua, G, Pawankar, R, Popov, Ta, Rabe, Kf, ROSADO PINTO, J, Scadding, Gk, Simons, Fe, Toskala, E, Valovirta, E, VAN CAUWENBERGE, P, Wang, Dy, Wickman, M, Yawn, Bp, Yorgancioglu, A, Yusuf, Om, Zar, H, ANNESI MAESANO, I, Bateman, Ed, BEN KHEDER, A, Boakye, Da, Bouchard, J, Burney, P, Busse, Ww, CHAN YEUNG, M, Chavannes, Nh, Chuchalin, A, Dolen, Wk, Emuzyte, R, Grouse, L, Humbert, M, Jackson, C, Johnston, Sl, Keith, Pk, Kemp, Jp, Klossek, Jm, LARENAS LINNEMANN, D, Lipworth, B, Malo, Jl, Marshall, Gd, Naspitz, C, Nekam, K, Niggemann, B, NIZANKOWSKA MOGILNICKA, E, Okamoto, Y, Orru, Mp, Potter, P, Price, D, Stoloff, Sw, Vandenplas, O, Viegi, G, Williams, D, WORLD HEALTH, Organization, and Galen, Allergen
Published: 2008

5. Clinical Pharmacology of New Histamiine H1 Receptor Antagonists

Author: Simons Fe and Keith J. Simons
Subjects: Pharmacology, Ebastine, Fexofenadine, Metabolic Clearance Rate, medicine.drug_class, Chemistry, Loratadine, Levocabastine, Structure-Activity Relationship, Intestinal Absorption, Astemizole, Acrivastine, Area Under Curve, Histamine H1 Antagonists, medicine, Humans, Pharmacology (medical), H1 antagonist, Half-Life, medicine.drug, Mizolastine
Abstract: The recently introduced H1 receptor antagonists ebastine, fexofenadine and mizolastine, and the relatively new H1 antagonists acrivastine, astemizole, azelastine, cetirizine, levocabastine and loratadine, are diverse in terms of chemical structure and clinical pharmacology, although they have similar efficacy in the treatment of patients with allergic disorders. Acrivastine is characterised by a short terminal elimination half-life (t1/2 beta) [1.7 hours] and an 8-hour duration of action. Astemizole and its metabolites, in contrast, have relatively long terminal t1/2 beta values; astemizole has a duration of action of at least 24 hours and is characterised by a long-lasting residual action after a short course of treatment. Azelastine, which has a half-life of approximately 22 hours, is primarily administered intranasally although an oral dosage formulation is used in some countries. Cetirizine is eliminated largely unchanged in the urine, has a terminal t1/2 beta of approximately 7 hours and a duration of action of at least 24 hours. Ebastine is extensively and rapidly metabolised to its active metabolite; carebastine, has a half-life of approximately 15 hours and duration of action of at least 24 hours. Fexofenadine, eliminated largely unchanged in the faeces and urine, has a terminal t1/2 beta of approximately 14 hours and duration of action of 24 hours, making it suitable for once or twice daily administration. Levocabastine has a terminal t1/2 beta of 35 to 40 hours regardless of the route of administration, but is only available as a topical application administered intranasally or ophthalmically in patients with allergic rhinoconjunctivitis. Loratadine is rapidly metabolised to an active metabolite descarboethoxyloratadine and has a 24-hour duration of action. Mizolastine has a terminal t1/2 beta of approximately 13 hours and duration of action of at least 24 hours. Most orally administered new H1 receptor antagonists are well absorbed and appear to be extensively distributed into body tissues; many are highly protein-bound. Most of the new H1 antagonists do not accumulate in tissues during repeated administration and have a residual action of less than 3 days after a short course has been completed. Tachyphylaxis, or loss of peripheral H1 receptor blocking activity during regular daily use, has not been found for any new H1 antagonist. Understanding the pharmacokinetics and pharmacodynamics of these new H1 antagonists provides the objective basis for selection of an appropriate dose and dosage interval and the rationale for modification in the dosage regimen that may be needed in special populations, including elderly patients, and those with hepatic dysfunction or renal dysfunction. The studies cited in this review provide the scientific foundation for using the new H1 antagonists with optimal effectiveness and safety.
Published: 1999

6. Learning Impairment and Allergic Rhinitis

Author: Simons Fe
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Rhinitis, Allergic, Perennial, Adolescent, Loratadine, Anti-Allergic Agents, medicine, Humans, Immunology and Allergy, Terfenadine, Child, Sinusitis, Adverse effect, rhinorrhea, Fexofenadine, Learning Disabilities, business.industry, Incidence, General Medicine, Prognosis, medicine.disease, Cetirizine, Child, Preschool, Quality of Life, Itching, medicine.symptom, business, medicine.drug
Abstract: Allergic rhinitis is underestimated as a cause of suffering and diminished quality of life in children and adolescents. If nasal symptoms such as itching, sneezing, rhinorrhea, and congestion are not well controlled during the day, they may contribute to learning problems during school hours. If these symptoms are not well controlled during the night, they may contribute to nocturnal sleep loss, secondary daytime fatigue and learning impairment. Even uncomplicated seasonal allergic rhinitis may be associated with reduced ability to learn, and the likelihood of learning problems may increase in severe perennial rhinitis or in rhinitis associated with complications such as sinusitis or eustachian tube dysfunction and conductive hearing loss. Also, many of the medications used to treat allergic rhinitis may cause central nervous system adverse effects and contribute to learning impairment. For some medications, such as inhaled glucocorticoids and decongestants, the potential effect on central nervous system function and learning has not been tested. For others such as H1-receptor antagonists (antihistamines), well-designed, prospective studies have been performed. The newer relatively nonsedating medications such as terfenadine, astemizole, loratadine, cetirizine, and fexofenadine have less potential to impair central nervous system function and learning than their predecessors.
Published: 1996

7. Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs

Author: Bousquet J, Schünemann HJ, Samolinski B, Demoly P, Baena-Cagnani CE, Bachert C, Bonini S, Boulet LP, Bousquet PJ, Brozek JL, Canonica GW, Casale TB, Cruz AA, Fokkens WJ, Fonseca JA, van Wijk RG, Grouse L, Haahtela T, Khaltaev N, Kuna P, Lockey RF, Lodrup Carlsen KC, Mullol J, Naclerio R, O'Hehir RE, Ohta K, Palkonen S, Papadopoulos NG, Passalacqua G, Pawankar R, Price D, Ryan D, Simons FE, Togias A, Williams D, Yorgancioglu A, Yusuf OM, Aberer W, Adachi M, Agache I, Aït-Khaled N, Akdis CA, Andrianarisoa A, Annesi-Maesano I, Ansotegui IJ, Baiardini I, Bateman ED, Bedbrook A, Beghé B, Beji M, Bel EH, Ben Kheder A, Bennoor KS, Bergmann KC, Berrissoul F, Bieber T, Bindslev Jensen C, Blaiss MS, Boner AL, Bouchard J, Braido F, Brightling CE, Bush A, Caballero F, Calderon MA, Calvo MA, Camargos PA, Caraballo LR, Carlsen KH, Carr W, Cepeda AM, Cesario A, Chavannes NH, Chen YZ, Chiriac AM, Chivato Pérez T, Chkhartishvili E, Ciprandi G, Costa DJ, Cox L, Custovic A, Dahl R, Darsow U, De Blay F, Deleanu D, Denburg JA, Devillier P, Didi T, Dokic D, Dolen WK, Douagui H, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, El-Meziane A, Emuzyte R, Fiocchi A, Fletcher M, Fukuda T, Gamkrelidze A, Gereda JE, González Diaz S, Gotua M, Guzmán MA, Hellings PW, Hellquist-Dahl B, Horak F, Hourihane JO, Howarth P, Humbert M, Ivancevich JC, Jackson C, Just J, Kalayci O, Kaliner MA, Kalyoncu AF, Keil T, Keith PK, Khayat G, Kim YY, Koffi N'goran B, Koppelman GH, Kowalski ML, Kull I, Kvedariene V, Larenas-Linnemann D, Le LT, Lemière C, Li J, Lieberman P, Lipworth B, Mahboub B, Makela MJ, Martin F, Marshall GD, Martinez FD, Masjedi MR, Maurer M, Mavale-Manuel S, Mazon A, Melen E, Meltzer EO, Mendez NH, Merk H, Mihaltan F, Mohammad Y, Morais-Almeida M, Muraro A, Nafti S, Namazova-Baranova L, Nekam K, Neou A, Niggemann B, Nizankowska-Mogilnicka E, Nyembue TD, Okamoto Y, Okubo K, Orru MP, Ouedraogo S, Ozdemir C, Panzner P, Pali-Schöll I, Park HS, Pigearias B, Pohl W, Popov TA, Postma DS, Potter P, Rabe KF, Ratomaharo J, Reitamo S, Ring J, Roberts R, Rogala B, Romano A, Roman Rodriguez M, Rosado-Pinto J, Rosenwasser L, Rottem M, Sanchez-Borges M, Scadding GK, Schmid-Grendelmeier P, Sheikh A, Sisul JC, Solé D, Sooronbaev T, Spicak V, Spranger O, Stein RT, Stoloff SW, Sunyer J, Szczeklik A, Todo-Bom A, Toskala E, Tremblay Y, Valenta R, Valero AL, Valeyre D, Valiulis A, Valovirta E, Van Cauwenberge P, Vandenplas O, van Weel C, Vichyanond P, Viegi G, Wang DY, Wickman M, Wöhrl S, Wright J, Yawn BP, Yiallouros PK, Zar HJ, Zernotti ME, Zhong N, Zidarn M, Zuberbier T, World Health Organization Collaborating Center for Asthma, and Rhinitis.
Published: 2012

8. Severe Chronic Allergic (and related) Diseases: a uniform approach- a MeDALL- GA(2)LEN-ARIA Position Paper

Author: WHO Collaborating Center for Asthma, Rhinitis, Bousquet, J, Anto, Jm, Demoly, P, Schünemann, Hj, Togias, A, Akdis, M, Auffray, C, Bachert, C, Bieber, T, Bousquet, Pj, Carlsen, Kh, Casale, Tb, Cruz, Aa, Keil, T, Lodrup Carlsen KC, Maurer, M, Ohta, K, Papadopoulos, Ng, Roman Rodriguez, M, Samolinski, B, Agache, I, Andrianarisoa, A, Ang, Cs, Annesi Maesano, I, Ballester, F, Baena Cagnani CE, Basagaña, X, Bateman, Ed, Bel, Eh, Bedbrook, A, Beghe', Bianca, Beji, M, Ben Kheder, A, Benet, M, Bennoor, Ks, Bergmann, Kc, Berrissoul, F, Bindslev Jensen, C, Bleecker, Er, Bonini, S, Boner, Al, Boulet, Lp, Brightling, Ce, Brozek, Jl, Bush, A, Busse, Ww, Camargos, Pa, Canonica, Gw, Carr, W, Cesario, A, Chen, Yz, Chiriac, Am, Costa, Dj, Cox, L, Custovic, A, Dahl, R, Darsow, U, Didi, T, Dolen, Wk, Douagui, H, Dubakiene, R, El Meziane, A, Fonseca, Ja, Fokkens, Wj, Fthenou, E, Gamkrelidze, A, Garcia Aymerich, J, Gerth van Wijk, R, Gimeno Santos, E, Guerra, S, Haahtela, T, Haddad, H, Hellings, Pw, Hellquist Dahl, B, Hohmann, C, Howarth, P, Hourihane, Jo, Humbert, M, Jacquemin, B, Just, J, Kalayci, O, Kaliner, Ma, Kauffmann, F, Kerkhof, M, Khayat, G, Koffi N'Goran, B, Kogevinas, M, Koppelman, Gh, Kowalski, Ml, Kull, I, Kuna, P, Larenas, D, Lavi, I, Le, Lt, Lieberman, P, Lipworth, B, Mahboub, B, Makela, Mj, Martin, F, Martinez, Fd, Marshall, Gd, Mazon, A, Melen, E, Meltzer, Eo, Mihaltan, F, Mohammad, Y, Mohammadi, A, Momas, I, Morais Almeida, M, Mullol, J, Muraro, A, Naclerio, R, Nafti, S, Namazova Baranova, L, Nawijn, Mc, Nyembue, Td, Oddie, S, O'Hehir, Re, Okamoto, Y, Orru, Mp, Ozdemir, C, Ouedraogo, Gs, Palkonen, S, Panzner, P, Passalacqua, G, Pawankar, R, Pigearias, B, Pin, I, Pinart, M, Pison, C, Popov, Ta, Porta, D, Postma, Ds, Price, D, Rabe, Kf, Ratomaharo, J, Reitamo, S, Rezagui, D, Ring, J, Roberts, R, Roca, J, Rogala, B, Romano, A, Rosado Pinto, J, Ryan, D, Sanchez Borges, M, Scadding, Gk, Sheikh, A, Simons, Fe, Siroux, V, Schmid Grendelmeier PD, Smit, Ha, Sooronbaev, T, Stein, Rt, Sterk, Pj, Sunyer, J, Terreehorst, I, Toskala, E, Tremblay, Y, Valenta, R, Valeyre, D, Vandenplas, O, van Weel, C, Vassilaki, M, Varraso, R, Viegi, G, Wang, Dy, Wickman, M, Williams, D, Wöhrl, S, Wright, J, Yorgancioglu, A, Yusuf, Om, Zar, Hj, Zernotti, Me, Zidarn, M, Zhong, N, Zuberbier, T., Beghe', B., Fthenou, E., Boudier, Anne, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), IMIM-Hospital del Mar, Generalitat de Catalunya, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER Epidemiologia y Salud Publica, CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona] (UPF), WHO Collaborating Center for Asthma and Rhinitis, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Génomique fonctionnelle et biologie systémique pour la santé, Institut des Sciences Biologiques du CNRS, Upper Airway Research Laboratory (URL), Ghent University Hospital, Department of Dermatology and Allergy, VU University Medical Center [Amsterdam], Department of Paediatrics, University of Oslo (UiO)-Oslo University Hospital [Oslo], Division of Allergy and Immunology, Department of Medicine, Creighton University, ProAR - FMB, Federal University of Bahia School of Medicine, Epidemiology and Health Economics, Instittute of Social Health-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Division of Respiratory Medicine and Allergology, Teikyo University School of Medicine, Allergy Department, 2nd Pediatric Clinic, Son Pisa Primary Care Centre, IB-Salut Balearic Health Service, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology, Faculty of Medicine-Transylvania University, Public Hospital Medical Service, Ministry of Health [Mozambique], Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Public Health Research (CSISP), University of Valencia, Respiratory Medicine, Università degli studi di Genova = University of Genoa (UniGe)-School of Specialization, Faculty of Medicine, Catholic University, Health Sciences Faculty, University of Cape Town, Department of Pulmonology, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Divisions of Human Genetics Infection, Inflammation and Repair, University of Southampton-School of Medicine, Service de Pneumologie Allergologie, Hôpital La Rabta [Tunis], Service de Pneumologie, Hôpital Abderrahmen Mami, National Asthma Centre, National Institute of Diseases of the Chest and Hospital (NIDCH), Pneumologie / Anesthésie - réanimation / Oxygénothérapie, Hôpital AKS Phnom Penh-Hôpital Provincial de Siemreap, Department of Dermatology and Allergy Center, Odense University Hospital, Center for Genomics and Personalized Medicine, Wake Forest University, Institute of Neurobiology and Molecular Medicine, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Verona = University of Verona (UNIVR), Institut de cardiologie et de pneumologie, Université Laval [Québec] (ULaval)-Centre Hospitalier de Laval (CH Laval), Department of Respiratory Medicine and Thoracic Surgery, University of Leicester-Institute for Lung Health, Department of Paediatric Respiratory Medicine, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], Department of Medicine, University of Wisconsin School of Medicine and Public Health, Department of Pediatrics, Universidade Federal de Minas Gerais [Belo Horizonte] (UFMG)-Medical School, Allergy & Respiratory Diseases, Università degli studi di Genova = University of Genoa (UniGe)-Department of Internal Medicine (DIMI), Allergy & Asthma Associates, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Deputy Scientific Director, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Department of Thoracic Surgery, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), National Cooperative Group of Pediatric Research on Asthma, Asthma Clinic and Education Center of the Capital Institute of Pediatrics, Service des Premiers Soins, Université Montpellier 1 (UM1), Osteopathic College of Medicine, Nova Southeastern University (NSU), Respiratory Research Group, University of Manchester [Manchester]-School of Translational Medicine, Department of Respiratory Diseases, Aarhus University Hospital, Department of Dermatology and Allergy Biederstein, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service de pneumologie, Centre hospitalier de la région d'Annecy, Service de pneumo-allergologie, Centre Hospitalo-Universitaire de Béni-Messous, Allergy Centre, Vilnius University Antakalnis Hospital, Société Marocaine des Maladies Respiratoires, Centre of Respiratory Diseases and Allergy-Centre commercial Nadia, Allergy Division, Hospital S. João-Centre for Research in Health Technologies and Information Systems (CINTESIS)-Biostatistics and Medical Informatics Department-Porto University Medical School, Department of Otorhinolaryngology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Social Medicine, University of Crete [Heraklion] (UOC)-Faculty of Medicine, Health Care, Minister Of Labour-Ministry of Labor, Health and Social Affairs, Section of Allergology, Erasmus Medical Centre, Epidemiology and Biostatistics Division, University of Arizona-Associate Research Scientist, Respiratory Sciences-Arizona Respiratory Center, Helsinki University Hospital-Skin and Allergy Hospital, Centre Hospitalier de Bigorre [Tarbes]-Association Franco-Libanaise de Pneumologie (AFLP), Department of Otorhinolaryngology, Head, and Neck Surgery, University Hospital Leuven, Engineering and the Environment, University of Southampton, Paediatrics and Child Health, University College Cork (UCC), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de l'Asthme et des Allergies [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pediatric Allergy and Asthma Unit, Ihsan Dogramaci Children's Hospital-Hacettepe University School of Medicine, Institute for Asthma and Allergy, George Washington University Medical School, Department of Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth (USJ)-Faculté de Médecine-Hôtel-Dieu de France, Service des Maladies Respiratoires, CHU de Cocody-UFR des Sciences Médicales, Pediatric Pulmonology, Allergology & Epidemiology, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Department of Clinical Immunology and Allergy, Medical University of Łódź (MUL)-Faculty ot Medicine, Centre for Allergy Research, Karolinska Institutet [Stockholm], Department of Clinical Science and Education, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Hospital Medica Sur, Physiology Department, University of Medicine and Pharmacy, Division of Allergy Immunology, Department of Medicine-The University of Tennessee Health Science Center [Memphis] (UTHSC), university of dundee asthma - allergic rhinitis - COPD - beta-2-adrenoceptor, University of Dundee, Pulmonary and allergy unit, American University of Sharjah-Rashid Hospital-Dubai Health Authority (DHA), Association Franco-Vietnamienne de Pneumologie (AFVP), Centre Hospitalier de Compiègne (CHC), Arizona Respiratory Center, Department of Medicine, Clinical Immunology and Allergy, University of Mississippi Medical Center (UMMC), Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Allergy & Asthma Medical Group & Research Center, University of California [San Diego] (UC San Diego), Pneumology Department, Marius Nasta Institute of Pneumology, Department of Internal Medicine, Tishreen University School of Medicine, Association Franco-Marocaine de Pathologie Thoracique (AFMAPATH), Collège National des Pneumologues Marocains, Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Immunoallergy Department, Hospital CUF Descobertas, Rhinology Unit & Smell Clinic, Universitat de Barcelona (UB)-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Allergy Unit, Università degli Studi di Padova = University of Padua (Unipd)-Department of Paediatrics, Section of Otolaryngology-Head & Neck Surgery (OHNS), University of Chicago, Clinique des maladies respiratoires, centre hospitalo-universitaire Mustapha Pacha d'Alger (CHUMA), Scientific Center for Children's Health, Russian Academy of Medical Sciences (RAMS), Laboratory of Allergology and Pulmonary Diseases, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG)-Department of Pathology and Medical Biology-GRIAC Research Institute, ENT Department, University of Kinshasa (UNIKIN), Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust-Bradford Institute for Health Research, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Chiba University Hospital, Asthme Rhinite allergique, Pharmacie, Division of Pediatric Allergy and Immunology, marmara university, Pédiatrie, Centre Hospitalier National Pédiatrique Charles de Gaulle (CHNP-CDG), European Federation of Allergy (EFA), Airways Diseases Patients' Associations, Department of Allergology and Clinical Immunology, Charles University [Prague] (CU)-Medical Faculty in Pilsen, Immunopharmacology, Nippon Medical School-Medical Research Council Clinical, Laboratoire du Sommeil et de l'Effort, Société de Pneumologie de Langue Française (SPLF)-Clinique St George, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinic of Allergy and Asthma, Medical University Sofia-Alexander's University Hospital, Regional Health Service - Lazio, Primary Care Respiratory Medicine, University of Aberdeen-Department of General Practice and Primary Care-General Practice Airways Group (GPIAG), Department of Pulmonary Medicine, Leiden University Medical Center (LUMC), Pneumalgia, Centre Hospitalier Regional-Espace Francophone de Pneumologie (EFP)-Société de Pneumologie de l'Océan Indien (SPOI), Association Franco-Algérienne de Pneumologie (AFAP), Espace Francophone de pneumologie de la SPLF, Department of Pneumology, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Hospital Clínic de Barcelona-Institut Clínic del Tórax (ICT)-CIBER de Enfermedades Respiratorias (CIBERES)-University of Barcelona, Allergology and Clinical Immunology, Medical University of Silesia (SUM)-Chair and Clinical Department of Internal Diseases, UCSC-Allergy Unit, Complesso Integrato Columbus-Department of Internal Medicine and Geriatrics, Hospital da Luz, Medical Centre, Woodbrook Medical Centre, Research Fellow, University of Aberdeen-Department of General Practice, Centro Médico Docente La Trinidad, Department of Pharmacology, University College of London [London] (UCL)-The Royal National Throat, Nose and Ear Hospital, Primary Care Research & Development, University of Edinburgh-Centre for Population Health Sciences, Section of Allergy & Clinical Immunology, University of Manitoba [Winnipeg]-Department of Pediatrics & Child Health, Allergy Unit - Department of Dermatology, Julius Center for Health Sciences and Primary Care, University Medical Center [Utrecht], National Centre of Cardiology and Internal Medicine, Ministry of Health Kyrgyz Republic, School of Medicine, Pontifícia Universidade Católica, Department of ENT and Pediatrics, Finnish Institute of Occupational Health, Department of Obstetrics and Gynaecology, Université Laval [Québec] (ULaval)-Faculty of Medicine, Christian Doppler Laboratory for Allergy Research, Medizinische Universität Wien = Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Department of Chest Medicine, Mont-Godinne Hospital-Catholic University of Louvain de Mont-Godinne, Department of Primary and Community Care, Radboud University Medical Center [Nijmegen], Epidemiology Unit, National Research Council (CNR)-Institute of Biomedicine and Molecular Immunology (IBIM), Pulmonary Environmental Epidemiology Unit, CNR Institute of Clinical Physiology, Department of Otolaryngology, National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, GLP Analytical Facility, School of Pharmacy, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna (MUW), Celal Bayar University School of Medicine, Allergy and Asthma Clinics, The Allergy and Asthma Institute, Department of Paediatrics and Child Health, Respiratory and Allergic Diseases, University Clinic of Respiratory and Allergic Diseases Golnik, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases-Guangzhou Medical College, Secretary General of the Global Allergy and Asthma European Network (GA2LEN), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], In collaboration with the WHO Collaborating Center for Asthma and Rhinitis, University of Genoa (UNIGE)-School of Specialization, CNR, Rome, Italy and Department of Medicine-University of Naples Federico II, University of Verona (UNIVR), Medical School-Federal University of Minas Gerais, University of Genoa (UNIGE)-Department of Internal Medicine (DIMI), University of California [Irvine] (UCI), University of California-University of California, Catholic University Rome, University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre Hospitalier de Bigorre (Tarbes)-Association Franco-Libanaise de Pneumologie (AFLP), CUF-Descobertas Hospital, Universita degli Studi di Padova-Department of Paediatrics, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Centro Medico-Docente La Trinidad, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]-Instittute of Social Health, Department of Internal Medicine (DIMI)-University of Genoa (UNIGE), Medical University of Silesia-Chair and Clinical Department of Internal Diseases, Dermatology, Internal Medicine, Immunology, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Research in Environmental Epidemiology ( CREAL ), Universitat Pompeu Fabra [Barcelona]-Catalunya ministerio de salud, Universitat Pompeu Fabra [Barcelona], WHO(OMS), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), National Institute of Allergy and Infectious Diseases [Bethesda], National Institutes of Health ( NIH ), Swiss Institute of Allergy and Asthma Research ( SIAF ), University of Zürich [Zürich] ( UZH ), Upper Airway Research Laboratory ( URL ), University Medical Center, University of Oslo ( UiO ) -Oslo University Hospital, Charite-Universitatsmedizin Berlin [Berlin]-Instittute of Social Health, Medical School-Charité - University Medicine Berlin, Medical University of Warsaw-Faculté de Pharmacie de Paris, Ministry of Health, Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Center for Public Health Research ( CSISP ), University of Genoa ( UNIGE ) -School of Specialization, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, University of Southampton [Southampton]-School of Medicine, Hôpital La Rabta [Tunis), Wake Forest University Health Sciences, CNR, Rome, Italy and Department of Medicine-Second University of Naples, Università degli Studi di Verona, Université Laval-l'Hôpital Laval, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, University of Genoa ( UNIGE ) -Department of Internal Medicine (DIMI), Southern California Research, Université Montpellier 1 ( UM1 ), Nova Southeastern University, Technische Universität München [München] ( TUM ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ), University of Crete ( UOC ) -Faculty of Medicine, University of Southampton [Southampton], UUniversity College Cork - National University of Ireland, Cork (UCC), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], University of Groningen [Groningen]-University Medical Center Groningen-Groningen Research Institute for Asthma and COPD (GRIAC), Université Saint-Joseph de Beyrouth ( USJ ) -Faculté de Médecine-Hôtel-Dieu de France, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Medical University of Łódź ( MUL ) -Faculty ot Medicine, Medical University of Łódź ( MUL ) -Barlicki University Hospital, Department of Medicine-University of Tennessee College for Medicine, Association Franco-Vietnamienne de Pneumologie ( AFVP ), University of Mississippi Medical Center, University of California [San Diego] ( UC San Diego ), Association Franco-Marocaine de Pathologie Thoracique ( AFMAPATH ), Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Université Paris Descartes - Paris 5 ( UPD5 ), Universitat de Barcelona ( UB ) -Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Department of Medicine-Hospital Clinic-ENT Department, Section of Otolaryngology-Head & Neck Surgery ( OHNS ), University of Groningen [Groningen]-University Medical Center Groningen-Department of Pathology and Medical Biology-GRIAC Research Institute, University Hospital of Kinshasa, European Federation of Allergy ( EFA ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Bioenergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of General Practice and Primary Care-General Practice Airways Group (GPIAG)-University of Aberdeen, Association Franco-Algérienne de Pneumologie ( AFAP ), Department of General Practice-University of Aberdeen, University College of London [London] ( UCL ) -The Royal National Throat, Nose and Ear Hospital, University Medical Center Utrecht, Faculty of Medicine-Laval University [Québec], Medical University of Vienna-Division of Immunopathology-Department of Pathophysiology and Allergy Research-Center for Pathophysiology, Infectiology and Immunology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, National University of Singapore ( NUS ) -Yong Loo Lin School of Medicine, Department of Dermatology Division of Immunology, Allergy and Infectious Diseases ( DIAID ), Secretary General of the Global Allergy and Asthma European Network ( GA2LEN ), Network of Excellence, Charité - Universitätsmedizin Berlin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Universiteit Leiden-Universiteit Leiden, and Medizinische Universität Wien = Medical University of Vienna
Subjects: MESH: Asthma, severity, MESH: Comorbidity, Comorbidity, Severity of Illness Index, urticaria, MESH : Chronic Disease, MESH: Practice Guidelines as Topic, MESH : Dermatitis, Atopic, MESH: Urticaria, risk, 216-31 [Rhinitis, atopy, allergen Int Arch Allergy Immunol. 2012,158(3)], atopic dermatitis, MESH : Rhinitis, MESH: Rhinitis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Effective primary care and public health [NCEBP 7], Immunoglobulin E - Asthma - Rhinitis - Rhinosinusitis - Urticaria - Atopic dermatitis, MESH : Practice Guidelines as Topic, Practice Guidelines as Topic, MESH : Comorbidity, MESH : Severity of Illness Index, IgE, MESH: Sinusitis, MESH : Urticaria, MESH: Hypersensitivity, macromolecular substances, MESH : Asthma, Dermatitis, Atopic, rhinitis, SDG 3 - Good Health and Well-being, MESH: Dermatitis, Atopic, MESH: Severity of Illness Index, Hypersensitivity, Humans, Sinusitis, rhinosinusitis, MESH : Hypersensitivity, MESH: Humans, MESH: Chronic Disease, MESH : Humans, Asthma, Atopic dermatitis, Immunoglobulin E, Rhinitis, Rhinosinusitis, Urticaria, asthma, allergy, MESH : Sinusitis, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, control
Abstract: Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies. Copyright (C) 2012 S. Karger AG, Basel
Published: 2012

9. Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GALEN)

Author: Bousquet, J, VAN CAUWENBERGE, P, AIT KHALED, N, Bachert, C, BAENA CAGNANI CE, Bouchard, J, Bunnag, C, Canonica, Giorgio, Carlsen, Kh, Chen, Yz, Cruz, Aa, Custovic, A, Demoly, P, Dubakiene, R, Durham, S, Fokkens, W, Howarth, P, Kemp, J, Kowalski, Ml, Kvedariene, V, Lipworth, B, Lockey, R, Lund, V, MAVALE MANUEL, S, Meltzer, Eo, Mullol, J, Naclerio, R, Nekam, K, Ohta, K, Papadopoulos, N, Passalacqua, Giovanni, Pawankar, R, Popov, T, Potter, P, Price, D, Scadding, G, Simons, Fe, Spicak, V, Valovirta, E, Wang, Dy, Yawn, B, and Yusuf, O.
Published: 2006

10. Requirements for medications commonly used in the treatment of allergic rhinitis. European Academy of Allergy and Clinical Immunology (EAACI), Allergic Rhinitis and its Impact on Asthma (ARIA)

Author: Bousquet, J, Van Cauwenberge, P, Bachert, C, Canonica, Giorgio, Demoly, P, Durham, Sr, Fokkens, W, Lockey, R, Meltzer, Eo, Mullol, J, Naclerio, Rm, Price, D, Simons, Fe, Vignola, Am, Warner, Jo, European Academy of Allergy, Clinical, Immunology, Allergic, Rhinitis, and its Impact on Asthma
Published: 2003

11. Clinical Pharmacology of H1-Antihistamines

Author: Simons Kj and Simons Fe
Subjects: medicine.medical_specialty, Clinical pharmacology, Pharmacokinetics, law, business.industry, Pharmacodynamics, Toxicity, medicine, Intensive care medicine, business, law.invention
Abstract: H1-antagonists have similar efﬁcacy in the treatment of patients with allergic rhinitis or urticaria; however, they are diverse with regard to their chemical structure (Fig. 1), clinical pharmacology, and potential for toxicity (1). The scientiﬁc foundation for using these medications with optimal effectiveness in all patient populations, including the very young, the elderly, and those with hepatic or renal dysfunction, or those taking other medications concurrently, is provided by results of pharmacokinetic and pharmacodynamic studies (2).
Published: 2002

12. A case-control study of the role of cold symptoms and other historical triggering factors in asthma exacerbations

Author: Sherlock C, Okada M, P. Warren, Jure Manfreda, Moira Chan-Yeung, Susan M. Tarlo, I. Broder, Allan Becker, Alexander C. Ferguson, Simons Fe, Paul Corey, and University of Manitoba
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Common Cold, Cold symptoms, Serology, Diseases of the respiratory system, immune system diseases, medicine, Humans, Intensive care medicine, Child, Asthma, Skin Tests, Asthma exacerbations, RC705-779, business.industry, Case-control study, food and beverages, Dust, Allergens, medicine.disease, respiratory tract diseases, Virus Diseases, Case-Control Studies, Immunology, Female, Tobacco Smoke Pollution, business
Abstract: BACKGROUND:Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study.OBJECTIVE:To assess the relative importance of colds and other nonclimatic historical triggers of asthma exacerbations.METHODS:One hundred and nineteen adults and children with asthma in two Canadian cities participated in a one-year study of the role of exacerbating factors in asthma. Among these, 36 pairs (21 adult, 15 children) completed the case-control study. Patients were considered cases if they developed an acute asthma exacerbation and notified the centre within 24 h to allow the completion of a questionnaire and viral studies (cultures of nasopharyngeal swabs and serology). Control people with asthma were matched for sex, age and area of residence, had no exacerbation during the preceding four weeks and participated within 48 h of the case patients.RESULTS:Case patients versus control patients had a mean age of 22 years versus 20 years, 50% versus 55% were male, and 92% versus 86% had at least one positive aeroallergen skin test. Cases were more likely to have taken regular inhaled steroids (63% versus 33%, PCONCLUSIONS:Symptomatic colds were the most common trigger of asthma exacerbations in the winter and spring, while a transient increase in dust exposure was also identified as a significant trigger. The association with chronic, passive smoke exposure and the use of inhaled costicosteroid medications likely reflected less stable pre-study asthma in those with exacerbations.
Published: 2000

13. How Do Rates of Asthma Exacerbations Compare in Pediatric and Adult Patients in TENOR?.

Author: Zeiger, RS, primary, Chipps, BE, additional, Haselkorn, T, additional, Rasouliyan, L, additional, Simons, FE, additional, and Fish, JE, additional
Published: 2009
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14. Timing the transfer of responsibilities for anaphylaxis recognition and use of an epinephrine auto-injector from adults to children and teenagers: pediatric allergists' perspective.

Author: Simons E, Sicherer SH, and Simons FE
Published: 2012

15. H1-antihistamine treatment in young atopic children: effect on urticaria.

Author: Simons FE and Early Prevention of Asthma in Atopic Children Study Group
Published: 2007
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16. SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department.

Author: Lieberman P, Decker W, Camargo CA Jr, Oconnor R, Oppenheimer J, Simons FE, Lieberman, Philip, Decker, Wyatt, Camargo, Carlos A Jr, Oconnor, Robert, Oppenheimer, John, and Simons, F Estelle
Published: 2007
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17. Self-injectable epinephrine for first-aid management of anaphylaxis [corrected] [published erratum appears in PEDIATRICS 2007 Jun;119(6):1271].

Author: Sicherer SH, Simons FE, and American Academy of Pediatrics. Section on Allergy and Immunology
Abstract: Anaphylaxis is a severe, potentially fatal systemic allergic reaction that is rapid in onset and may cause death. Epinephrine is the primary medical therapy, and it must be administered promptly. This clinical report focuses on practical issues concerning the administration of self-injectable epinephrine for first-aid treatment of anaphylaxis in the community. The recommended epinephrine dose for anaphylaxis in children, based primarily on anecdotal evidence, is 0.01 mg/kg, up to 0.30 mg. Intramuscular injection of epinephrine into the lateral thigh (vastus lateralis) is the preferred route for therapy in first-aid treatment. Epinephrine autoinjectors are currently available in only 2 fixed doses: 0.15 and 0.30 mg. On the basis of current, albeit limited, data, it seems reasonable to recommend autoinjectors with 0.15 mg of epinephrine for otherwise healthy young children who weigh 10 to 25 kg (22-55 lb) and autoinjectors with 0.30 mg of epinephrine for those who weigh approximately 25 kg (55 lb) or more; however, specific clinical circumstances must be considered in these decisions. This report also describes several quandaries in regard to management, including the selection of dose, indications for prescribing an autoinjector, and decisions regarding when to inject epinephrine. Effective care for individuals at risk of anaphylaxis requires a comprehensive management approach involving families, allergic children, schools, camps, and other youth organizations. Risk reduction entails confirmation of the trigger, discussion of avoidance of the relevant allergen, a written individualized emergency anaphylaxis action plan, and education of supervising adults with regard to recognition and treatment of anaphylaxis. [ABSTRACT FROM AUTHOR]
Published: 2007
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18. Tolerance to the bronchoprotective effect of salmeterol in adolescents with exercise-induced asthma using concurrent inhaled glucocorticoid treatment.

Author: Simons FE, Gerstner TV, and Cheang MS
Abstract: OBJECTIVES: The long-acting beta2-adrenergic agonist salmeterol prevents exercise-induced asthma, but tolerance may develop to its bronchoprotective effect. We wanted to ascertain if the development of tolerance could be prevented by using a low-dose treatment regimen of 50 microg once daily, instead of the usual dose of 50 microg twice daily, in adolescents receiving regular glucocorticoid inhalations. Methods. In a randomized, double-blind, 2x28-day crossover study, we administered salmeterol (50 microg) or placebo once daily via a metered-dose inhaler and Nebulizer Chronolog device to monitor compliance. Exercise challenge tests were performed 1 and 9 hours after salmeterol or placebo inhalation on the 1st and 28th day of each treatment period. The primary outcome variable was the maximum decrease in percent predicted FEV1 postexercise. RESULTS: Fourteen subjects with a mean age of 13.1 years completed the study. The first dose of salmeterol had an excellent bronchoprotective effect against exercise-induced asthma at 1 and 9 hours. After the 28th consecutive daily dose of salmeterol, the bronchoprotective effect was significantly greater than that of placebo at 1 hour, but not at 9 hours. CONCLUSIONS: We conclude that a single 50-microg dose of salmeterol has an excellent protective effect against exercise-induced asthma for at least 9 hours, but that this effect may wane during regular once-daily salmeterol treatment, despite the reduced frequency of dosing and despite concomitant use of inhaled glucocorticoids. [ABSTRACT FROM AUTHOR]
Published: 1997
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19. The Pharmacokinetics of Theophylline in an Infant with Hepatic Failure1

Author: Simons Kj, Haworth Jc, Simons Fe, and George H. Luciuk
Subjects: medicine.medical_specialty, business.industry, Liter, Hereditary tyrosinemia, chemistry.chemical_compound, Endocrinology, Pharmacokinetics, chemistry, Internal medicine, medicine, Pharmacology (medical), Theophylline, General Pharmacology, Toxicology and Pharmaceutics, Liver dysfunction, Urine sample, Caffeine, business, Clearance rate, medicine.drug
Abstract: In a 6 1/2-month-old infant with hepatic failure secondary to hereditary tyrosinemia, the theophylline clearance rate of 0.016 liter/kg/h was reduced for age and the serum half-life was prolonged to 18.0 h. Theophylline, 3.4 micrograms/ml, and caffeine, 2.2 micrograms/ml, were identified in a urine sample obtained 48 h after the test dose of theophylline, but no 1-methyluric acid, 1,3-dimethyluric acid or 3-methylxanthine were detected. This is the first infant with liver dysfunction and impaired theophylline disposition to be reported.
Published: 1982

20. The pharmacokinetics of dihydroxypropyltheophylline: a basis for rational therapy

Author: Bierman Cw, K.J. Simons, and Simons Fe
Subjects: Adult, Male, Adolescent, Immunology, Administration, Oral, Biological Availability, Pharmacology, Injections, Intramuscular, Route of administration, Dyphylline, Pharmacokinetics, Theophylline, medicine, Immunology and Allergy, Humans, Dose-Response Relationship, Drug, business.industry, Half-life, Middle Aged, Asthma, Bioavailability, Kinetics, Anesthesia, Female, Intramuscular injection, business, Biological availability, medicine.drug, Half-Life
Abstract: Dihydroxypropyltheophylline (dyphylline) was administered in a single dose on 7 different days to 7 normal subjects; 5 mg/kg was given by intramuscular injection and oral tablet; 10 mg/kg was given by these routes and also in 3 different liquid formulations. Dyphylline is rapidly absorbed, and bioavailability is independent of route of administration or formulation. The pharmacokinetics of dyphylline do not appear to be dose-dependent in the dosage range studied. The mean half-life of dyphylline is 2.11 +/- 0.36 hr; because of its short half-life and unproved efficacy, current dosage recommendations for dyphylline must be revised greatly. Further efficacy trials utilizing the pharmacokinetic data from this study are essential.
Published: 1975

21. Comparison of the mosquito saliva-capture enzyme-linked immunosorbent assay and the UniCAP test in the diagnosis of mosquito allergy.

Author: Wang Q, Beckett A, Simons FE, and Peng Z
Published: 2007
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22. Evaluation of the National Heart, Lung, and Blood Institute guidelines impairment domain for classifying asthma control and predicting asthma exacerbations.

Author: Zeiger RS, Yegin A, Simons FE, Haselkorn T, Rasouliyan L, Szefler SJ, Chipps BE, and TENOR Study Group
Published: 2012

23. Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis.

Author: Vadas P, Gold M, Perelman B, Liss GM, Lack G, Blyth T, Simons FE, Simons KJ, Cass D, and Yeung J
Published: 2008

24. Marginally Stable Equilibria in Critical Ecosystems

Author: Chiara Cammarota, Giulio Biroli, Guy Bunin, Institut de Physique Théorique - UMR CNRS 3681 (IPHT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Massachusetts Institute of Technology (MIT), Department of Physics [Haifa], Technion - Israel Institute of Technology [Haifa], King‘s College London, Grant from the Simons Foundation number 454935 (G.B.), Simons FE, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and De Laborderie, Emmanuelle
Subjects: Physics, [PHYS]Physics [physics], Ecology, self organized criticality, stability, Statistical Mechanics (cond-mat.stat-mech), Complex system, Populations and Evolution (q-bio.PE), General Physics and Astronomy, FOS: Physical sciences, Theoretical ecology, 01 natural sciences, Stability (probability), Instability, [PHYS] Physics [physics], 010305 fluids & plasmas, FOS: Biological sciences, 0103 physical sciences, Canonical model, Statistical physics, 010306 general physics, Quantitative Biology - Populations and Evolution, Randomness, Condensed Matter - Statistical Mechanics, Marginal stability, Simple (philosophy)
Abstract: In this work we study the stability of the equilibria reached by ecosystems formed by a large number of species. The model we focus on are Lotka-Volterra equations with symmetric random interactions. Our theoretical analysis, confirmed by our numerical studies, shows that for strong and heterogeneous interactions the system displays multiple equilibria which are all marginally stable. This property allows us to obtain general identities between diversity and single species responses, which generalize and saturate May's bound. By connecting the model to systems studied in condensed matter physics, we show that the multiple equilibria regime is analogous to a critical spin-glass phase. This relation provides a new perspective as to why many systems in several different fields appear to be poised at the edge of stability and also suggests new experimental ways to probe marginal stability. Many complex systems in Nature organize in states that are poised just at the edge of stability. The growing evidence comes from physics [1], biology [2], ecology [3], neuroscience [4, 5] and economy [6]. One important common trait of all examples is that they are formed by strongly interacting units—species, neurons, agents and particles depending on the situation. The possible explanations of such phenomenon are varied. They include the need for flexibility and adaptiveness to time-varying conditions [2, 7], balance between functionality and stability [7], self-organized criticality [8], self-organized instability [9], and continuous constraints satisfaction [1]. Here we address this problem focusing on generalized Lotka-Volterra (LV) equations. They provide a simple and general setting to study assemblies of interacting degrees of freedom; as such they are used in several fields [10–13]. In particular, they provide a canonical model for ecosystems, with growing connections to systems across biology [10, 11, 14]. The study of stability of equilibria and their properties using LV equations and generalizations has become a very active research subject. Several important results were obtained recently; in particular general techniques to count the number of equilibria and their properties have been developed [15], and criticality and glassiness have been found to be emergent properties of ecosystems [16–18]. Our approach unifies these different perspectives and, by a mapping to condensed matter systems, reveal their generality beyond LV models. Henceforth, in order to describe it, we shall use the terminology employed in theoretical ecology. In the model we consider, an ecological community is assembled from a pool of available species. We focus on the case relevant for the examples cited above, and in many other situations, when the number of species is large. Since the detailed parameters of all interactions are not known in the majority of cases, and in any case not all details are expected to matter [19], we follow the long tradition pioneered by May in ecology [20] and Wigner in physics [21], and sample the interactions randomly. However , we go beyond May's classical work since randomness is here introduced at the level of interactions between all possible species, while the community self-organizes by choosing which species are present. In other words, the number and identity of the species that are present in the community is selected dynamically [22, 23]. Understanding the emergent stability of the equilibria reached dynamically and its dependence on the external parameters is the main purpose of this work. We find, in agreement with [16, 18, 24], that when the interactions are weak or highly uniform, only one equilibrium is present and is determined mainly by self-regulation within each species. For stronger and more heterogeneous interactions, multiple equilibria emerge. Our main result is that when this happens, all possible states of the system are close to be marginally stable for large number of species and this determines the diversity of the ecosystem, see Fig. 1. Marginal stability has several important consequences, in particular it leads to extreme susceptibility to small perturbations. This situation is referred as " critical " in the physics literature [25]. May famously suggested that complexity and interactions limit the stability of ecosystems [20]. Our results provide a complementary perspective: complex ecological communities reduce dynamically their instability through a reduction of the possible number of surviving species, i.e. diversity, and eventually reach a marginally stable state saturating May's bound. Since this phenomenon stems from a dynamical process, it holds for a broad range of system parameters. It is robust against a range of variations in the model, including different functional forms of responses and interactions, as well as noise. Although in many physical cases criticality
Published: 2017

25. Practical guide to skin prick tests in allergy to aeroallergens

Author: Bousquet, J, Heinzerling, L, Bachert, C, Papadopoulos, NG, Bousquet, PJ, Burney, PG, Canonica, GW, Carlsen, KH, Cox, L, Haahtela, T, Carlsen, KCL, Price, D, Samolinski, B, Simons, FER, Wickman, M, Annesi-Maesano, I, Baena-Cagnani, CE, Bergmann, KC, Bindslev-Jensen, C, Casale, TB, Chiriac, A, Cruz, AA, Dubakiene, R, Durham, SR, Fokkens, WJ, Gerth van Wijk, Roy, Kalayci, O, Kowalski, ML, Mari, A, Mullol, J, Nazamova-Baranova, L, O'Hehir, RE, Ohta, K, Panzner, P, Passalacqua, G, Ring, J, Rogala, B, Romano, A, Ryan, D, Schmid-Grendelmeier, P, Todo-Bom, A, Valenta, R, Woehrl, S, Yusuf, OM, Zuberbier, T, Demoly, P, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Bousquet J, Heinzerling L, Bindslev-Jensen C, Casale TB, Bachert C, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Lodrup Carlsen KC, Kowalski ML, Mari A, Mullol J, Papadopoulos NG, Nazamova-Baranova L, O'Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Price D, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Bousquet PJ, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Samolinski B, Demoly P, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Simons FE, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, AII - Amsterdam institute for Infection and Immunity, Ear, Nose and Throat, University of Zurich, Bousquet, J, Dermatology, and Internal Medicine
Subjects: 2403 Immunology, Air Pollutants, 2723 Immunology and Allergy, Hypersensitivity, 10177 Dermatology Clinic, Humans, 610 Medicine & health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Allergens, Skin Tests
Abstract: International audience; To cite this article: Bousquet J, Heinzerling L, Bachert C, Papadopoulos NG, Bousquet PJ, Burney PG, Canonica GW, Carlsen KH, Cox L, Haahtela T, Lodrup Carlsen KC, Price D, Samolinski B, Simons FER, Wickman M, Annesi-Maesano I, Baena-Cagnani CE, Bergmann KC, Bindslev-Jensen C, Casale TB, Chiriac A, Cruz AA, Dubakiene R, Durham SR, Fokkens WJ, Gerth-van-Wijk R, Kalayci O, Kowalski ML, Mari A, Mullol J, Nazamova-Baranova L, O'Hehir RE, Ohta K, Panzner P, Passalacqua G, Ring J, Rogala B, Romano A, Ryan D, Schmid-Grendelmeier P, Todo-Bom A, Valenta R, Woehrl S, Yusuf OM, Zuberbier T, Demoly P. Practical guide to skin prick tests in allergy to aeroallergens. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02728.x ABSTRACT: This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.
Published: 2011

26. Consensus group on new-generation antihistamines (CONGA): present status and recommendations

Author: Holgate, St, Canonica, Gw, Simons, Fer, Taglialatela, Maurizio, Tharp, M, Timmerman, H, Yanai, K, Baena Cagnani CE, Naclerio, Rm, Scadding, Gk, Taglialatela, M, Morganroth, J, Potter, P, O'Hehir, Re, Renwick, Ag, Testa, B, Hindmarch, I, Ramaeker, R, Wong, Df, Leurs, R, Panula, P, Hough, L., Holgate, St, Canonica, Gw, Simons, Fe, Taglialatela, Maurizio, Tharp, M, Timmerman, H, and Yanai, K.
Subjects: medicine.medical_specialty, Heart Diseases, business.industry, Group (mathematics), Immunology, Treatment outcome, Anti-Inflammatory Agents, Histamine Antagonists, MEDLINE, Alternative medicine, Pharmacology, Treatment Outcome, Central Nervous System Diseases, Family medicine, Histamine H1 Antagonists, Hypersensitivity, Humans, Immunology and Allergy, Medicine, Drug Interactions, business
Published: 2003

27. Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS.

Author: Courbis AL, Murray RB, Arnavielhe S, Caimmi D, Bedbrook A, Van Eerd M, De Vries G, Dray G, Agache I, Morais-Almeida M, Bachert C, Bergmann KC, Bosnic-Anticevich S, Brozek J, Bucca C, Camargos P, Canonica GW, Carr W, Casale T, Fonseca JA, Haahtela T, Kalayci O, Klimek L, Kuna P, Kvedariene V, Larenas Linnemann D, Lieberman P, Mullol J, Ohehir R, Papadopoulos N, Price D, Ryan D, Samolinski B, Simons FE, Tomazic P, Triggiani M, Valiulis A, Valovirta E, Wagenmann M, Wickman M, Yorgancioglu A, and Bousquet J
Subjects: Disease Management, Evidence-Based Practice, Humans, Rhinitis, Allergic immunology, Rhinitis, Allergic therapy, Smartphone, Telemedicine, User-Computer Interface, Decision Support Systems, Clinical standards, Mobile Applications, Rhinitis, Allergic diagnosis
Abstract: Background: Allergic rhinitis (AR) management has changed in recent years following the switch from the concept of disease severity to the concept of disease control, publication of the AR clinical decision support system (CDSS) and development of mobile health (m-health) tools for patients (eg Allergy Diary). The Allergy Diary Companion app for healthcare providers is currently being developed and will be launched in 2018. It incorporates the AR CDSS to provide evidence-based treatment recommendations, linking all key stakeholders in AR management., Objective: To produce an electronic version of the AR CDSS (e-CDSS) for incorporation into the Allergy Diary Companion, to describe the app interfaces used to collect information necessary to inform the e-CDSS and to summarize some key features of the Allergy Diary Companion., Methods: The steps involved in producing the e-CDSS and incorporating it into the Allergy Diary Companion were (a) generation of treatment management scenarios; (b) expert consensus on treatment recommendations; (c) generation of electronic decisional algorithms to describe all AR CDSS scenarios; (d) digitization of these algorithms to form the e-CDSS; and (e) embedding the e-CDSS into the app to permit easy user e-CDSS interfacing., Results: Key experts in the AR field agreed on the AR CDSS approach to AR management and on specific treatment recommendations provided by Allergy Diary Companion. Based on this consensus, decision processes were developed and programmed into the Allergy Diary Companion using Titanium Appcelerator (JavaScript) for IOS tablets. To our knowledge, this is the first time the development of any m-health tool has been described in this transparent and detailed way, providing confidence, not only in the app, but also in the provided management recommendations., Conclusion: The Allergy Diary Companion for providers provides guideline and expert-endorsed AR management recommendations. [MASK paper No 32]., (© 2018 John Wiley & Sons Ltd.)
Published: 2018
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28. Fatal anaphylaxis registries data support changes in the who anaphylaxis mortality coding rules.

Author: Tanno LK, Simons FE, Annesi-Maesano I, Calderon MA, Aymé S, and Demoly P
Subjects: Humans, Anaphylaxis mortality, Clinical Coding methods, Registries, World Health Organization
Abstract: Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. The difficulty of coding anaphylaxis fatalities under the World Health Organization (WHO) International Classification of Diseases (ICD) system is recognized as an important reason for under-notification of anaphylaxis deaths. On current death certificates, a limited number of ICD codes are valid as underlying causes of death, and death certificates do not include the word anaphylaxis per se. In this review, we provide evidences supporting the need for changes in WHO mortality coding rules and call for addition of anaphylaxis as an underlying cause of death on international death certificates. This publication will be included in support of a formal request to the WHO as a formal request for this move taking the 11 th ICD revision.
Published: 2017
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29. Decreasing the undernotification of anaphylaxis deaths in Brazil through the International Classification of Diseases (ICD)-11 revision.

Author: Tanno LK, Bierrenbach AL, Calderon MA, Sheikh A, Simons FE, and Demoly P
Subjects: Adolescent, Adult, Aged, Anaphylaxis diagnosis, Anaphylaxis mortality, Brazil epidemiology, Cause of Death, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, International Classification of Diseases, Male, Middle Aged, Young Adult, Anaphylaxis epidemiology, Disease Notification statistics & numerical data
Abstract: Background: In 2012, an analysis of the Brazilian mortality database demonstrated undernotification of anaphylaxis deaths due, at least in part, to difficult coding under the International Classification of Diseases (ICD)-10. This work triggered a cascade of strategic international actions supported by the Joint Allergy Academies and the ICD World Health Organization (WHO) representatives to update the classifications of allergic disorders for the ICD-11 revision. These efforts have resulted in the construction of the new 'Allergic and hypersensitivity conditions' section under the 'Disorders of the Immune system' chapter., Objective: To analyze the capacity of the new ICD-11 revision to capture anaphylaxis deaths., Methods: We re-estimated the anaphylaxis deaths that occurred in Brazil during the period 2008 to 2010, utilizing this new framework and the database of the Brazilian mortality information system that had initially been extracted in May 2011. However, in 2016, a manual review of each of the 3638 records was performed., Results: We identified 639 anaphylaxis deaths, of which 95% were classified as 'definitive anaphylaxis deaths'. In contrast to the 2012 published data, we found a higher number of cases; moreover, all 606 definitive anaphylaxis deaths would be considered as underlying causes of death utilizing the ICD-11 revision., Conclusion: This study is the first example of how the new 'Allergic and hypersensitivity conditions' section of the forthcoming ICD-11 can improve the quality of official vital statistics data and the visibility of an important public health concern. This research will facilitate comprehensive, comparable population-based epidemiologic data collection on anaphylaxis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2017
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30. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle.

Author: Bousquet J, Hellings PW, Agache I, Bedbrook A, Bachert C, Bergmann KC, Bewick M, Bindslev-Jensen C, Bosnic-Anticevitch S, Bucca C, Caimmi DP, Camargos PA, Canonica GW, Casale T, Chavannes NH, Cruz AA, De Carlo G, Dahl R, Demoly P, Devillier P, Fonseca J, Fokkens WJ, Guldemond NA, Haahtela T, Illario M, Just J, Keil T, Klimek L, Kuna P, Larenas-Linnemann D, Morais-Almeida M, Mullol J, Murray R, Naclerio R, O'Hehir RE, Papadopoulos NG, Pawankar R, Potter P, Ryan D, Samolinski B, Schunemann HJ, Sheikh A, Simons FE, Stellato C, Todo-Bom A, Tomazic PV, Valiulis A, Valovirta E, Ventura MT, Wickman M, Young I, Yorgancioglu A, Zuberbier T, Aberer W, Akdis CA, Akdis M, Annesi-Maesano I, Ankri J, Ansotegui IJ, Anto JM, Arnavielhe S, Asarnoj A, Arshad H, Avolio F, Baiardini I, Barbara C, Barbagallo M, Bateman ED, Beghé B, Bel EH, Bennoor KS, Benson M, Białoszewski AZ, Bieber T, Bjermer L, Blain H, Blasi F, Boner AL, Bonini M, Bonini S, Bosse I, Bouchard J, Boulet LP, Bourret R, Bousquet PJ, Braido F, Briggs AH, Brightling CE, Brozek J, Buhl R, Bunu C, Burte E, Bush A, Caballero-Fonseca F, Calderon MA, Camuzat T, Cardona V, Carreiro-Martins P, Carriazo AM, Carlsen KH, Carr W, Cepeda Sarabia AM, Cesari M, Chatzi L, Chiron R, Chivato T, Chkhartishvili E, Chuchalin AG, Chung KF, Ciprandi G, de Sousa JC, Cox L, Crooks G, Custovic A, Dahlen SE, Darsow U, Dedeu T, Deleanu D, Denburg JA, De Vries G, Didier A, Dinh-Xuan AT, Dokic D, Douagui H, Dray G, Dubakiene R, Durham SR, Du Toit G, Dykewicz MS, Eklund P, El-Gamal Y, Ellers E, Emuzyte R, Farrell J, Fink Wagner A, Fiocchi A, Fletcher M, Forastiere F, Gaga M, Gamkrelidze A, Gemicioğlu B, Gereda JE, van Wick RG, González Diaz S, Grisle I, Grouse L, Gutter Z, Guzmán MA, Hellquist-Dahl B, Heinrich J, Horak F, Hourihane JO, Humbert M, Hyland M, Iaccarino G, Jares EJ, Jeandel C, Johnston SL, Joos G, Jonquet O, Jung KS, Jutel M, Kaidashev I, Khaitov M, Kalayci O, Kalyoncu AF, Kardas P, Keith PK, Kerkhof M, Kerstjens HA, Khaltaev N, Kogevinas M, Kolek V, Koppelman GH, Kowalski ML, Kuitunen M, Kull I, Kvedariene V, Lambrecht B, Lau S, Laune D, Le LT, Lieberman P, Lipworth B, Li J, Lodrup Carlsen KC, Louis R, Lupinek C, MacNee W, Magar Y, Magnan A, Mahboub B, Maier D, Majer I, Malva J, Manning P, De Manuel Keenoy E, Marshall GD, Masjedi MR, Mathieu-Dupas E, Maurer M, Mavale-Manuel S, Melén E, Melo-Gomes E, Meltzer EO, Mercier J, Merk H, Miculinic N, Mihaltan F, Milenkovic B, Millot-Keurinck J, Mohammad Y, Momas I, Mösges R, Muraro A, Namazova-Baranova L, Nadif R, Neffen H, Nekam K, Nieto A, Niggemann B, Nogueira-Silva L, Nogues M, Nyembue TD, Ohta K, Okamoto Y, Okubo K, Olive-Elias M, Ouedraogo S, Paggiaro P, Pali-Schöll I, Palkonen S, Panzner P, Papi A, Park HS, Passalacqua G, Pedersen S, Pereira AM, Pfaar O, Picard R, Pigearias B, Pin I, Plavec D, Pohl W, Popov TA, Portejoie F, Postma D, Poulsen LK, Price D, Rabe KF, Raciborski F, Roberts G, Robalo-Cordeiro C, Rodenas F, Rodriguez-Mañas L, Rolland C, Roman Rodriguez M, Romano A, Rosado-Pinto J, Rosario N, Rottem M, Sanchez-Borges M, Sastre-Dominguez J, Scadding GK, Scichilone N, Schmid-Grendelmeier P, Serrano E, Shields M, Siroux V, Sisul JC, Skrindo I, Smit HA, Solé D, Sooronbaev T, Spranger O, Stelmach R, Sterk PJ, Strandberg T, Sunyer J, Thijs C, Triggiani M, Valenta R, Valero A, van Eerd M, van Ganse E, van Hague M, Vandenplas O, Varona LL, Vellas B, Vezzani G, Vazankari T, Viegi G, Vontetsianos T, Wagenmann M, Walker S, Wang DY, Wahn U, Werfel T, Whalley B, Williams DM, Williams S, Wilson N, Wright J, Yawn BP, Yiallouros PK, Yusuf OM, Zaidi A, Zar HJ, Zernotti ME, Zhang L, Zhong N, and Zidarn M
Abstract: The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA ( Contre les Maladies Chroniques pour un Vieillissement Actif )-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
Published: 2016
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31. Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

Author: Bousquet J, Farrell J, Crooks G, Hellings P, Bel EH, Bewick M, Chavannes NH, de Sousa JC, Cruz AA, Haahtela T, Joos G, Khaltaev N, Malva J, Muraro A, Nogues M, Palkonen S, Pedersen S, Robalo-Cordeiro C, Samolinski B, Strandberg T, Valiulis A, Yorgancioglu A, Zuberbier T, Bedbrook A, Aberer W, Adachi M, Agusti A, Akdis CA, Akdis M, Ankri J, Alonso A, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielhe S, Arshad H, Bai C, Baiardini I, Bachert C, Baigenzhin AK, Barbara C, Bateman ED, Beghé B, Kheder AB, Bennoor KS, Benson M, Bergmann KC, Bieber T, Bindslev-Jensen C, Bjermer L, Blain H, Blasi F, Boner AL, Bonini M, Bonini S, Bosnic-Anticevitch S, Boulet LP, Bourret R, Bousquet PJ, Braido F, Briggs AH, Brightling CE, Brozek J, Buhl R, Burney PG, Bush A, Caballero-Fonseca F, Caimmi D, Calderon MA, Calverley PM, Camargos PA, Canonica GW, Camuzat T, Carlsen KH, Carr W, Carriazo A, Casale T, Cepeda Sarabia AM, Chatzi L, Chen YZ, Chiron R, Chkhartishvili E, Chuchalin AG, Chung KF, Ciprandi G, Cirule I, Cox L, Costa DJ, Custovic A, Dahl R, Dahlen SE, Darsow U, De Carlo G, De Blay F, Dedeu T, Deleanu D, De Manuel Keenoy E, Demoly P, Denburg JA, Devillier P, Didier A, Dinh-Xuan AT, Djukanovic R, Dokic D, Douagui H, Dray G, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, Emuzyte R, Fabbri LM, Fletcher M, Fiocchi A, Fink Wagner A, Fonseca J, Fokkens WJ, Forastiere F, Frith P, Gaga M, Gamkrelidze A, Garces J, Garcia-Aymerich J, Gemicioğlu B, Gereda JE, González Diaz S, Gotua M, Grisle I, Grouse L, Gutter Z, Guzmán MA, Heaney LG, Hellquist-Dahl B, Henderson D, Hendry A, Heinrich J, Heve D, Horak F, Hourihane JO, Howarth P, Humbert M, Hyland ME, Illario M, Ivancevich JC, Jardim JR, Jares EJ, Jeandel C, Jenkins C, Johnston SL, Jonquet O, Julge K, Jung KS, Just J, Kaidashev I, Kaitov MR, Kalayci O, Kalyoncu AF, Keil T, Keith PK, Klimek L, Koffi N'Goran B, Kolek V, Koppelman GH, Kowalski ML, Kull I, Kuna P, Kvedariene V, Lambrecht B, Lau S, Larenas-Linnemann D, Laune D, Le LT, Lieberman P, Lipworth B, Li J, Lodrup Carlsen K, Louis R, MacNee W, Magard Y, Magnan A, Mahboub B, Mair A, Majer I, Makela MJ, Manning P, Mara S, Marshall GD, Masjedi MR, Matignon P, Maurer M, Mavale-Manuel S, Melén E, Melo-Gomes E, Meltzer EO, Menzies-Gow A, Merk H, Michel JP, Miculinic N, Mihaltan F, Milenkovic B, Mohammad GM, Molimard M, Momas I, Montilla-Santana A, Morais-Almeida M, Morgan M, Mösges R, Mullol J, Nafti S, Namazova-Baranova L, Naclerio R, Neou A, Neffen H, Nekam K, Niggemann B, Ninot G, Nyembue TD, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Ouedraogo S, Paggiaro P, Pali-Schöll I, Panzner P, Papadopoulos N, Papi A, Park HS, Passalacqua G, Pavord I, Pawankar R, Pengelly R, Pfaar O, Picard R, Pigearias B, Pin I, Plavec D, Poethig D, Pohl W, Popov TA, Portejoie F, Potter P, Postma D, Price D, Rabe KF, Raciborski F, Radier Pontal F, Repka-Ramirez S, Reitamo S, Rennard S, Rodenas F, Roberts J, Roca J, Rodriguez Mañas L, Rolland C, Roman Rodriguez M, Romano A, Rosado-Pinto J, Rosario N, Rosenwasser L, Rottem M, Ryan D, Sanchez-Borges M, Scadding GK, Schunemann HJ, Serrano E, Schmid-Grendelmeier P, Schulz H, Sheikh A, Shields M, Siafakas N, Sibille Y, Similowski T, Simons FE, Sisul JC, Skrindo I, Smit HA, Solé D, Sooronbaev T, Spranger O, Stelmach R, Sterk PJ, Sunyer J, Thijs C, To T, Todo-Bom A, Triggiani M, Valenta R, Valero AL, Valia E, Valovirta E, Van Ganse E, van Hage M, Vandenplas O, Vasankari T, Vellas B, Vestbo J, Vezzani G, Vichyanond P, Viegi G, Vogelmeier C, Vontetsianos T, Wagenmann M, Wallaert B, Walker S, Wang DY, Wahn U, Wickman M, Williams DM, Williams S, Wright J, Yawn BP, Yiallouros PK, Yusuf OM, Zaidi A, Zar HJ, Zernotti ME, Zhang L, Zhong N, Zidarn M, and Mercier J
Abstract: Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
Published: 2016
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32. Lean healthcare from a change management perspective.

Author: van Rossum L, Aij KH, Simons FE, van der Eng N, and Ten Have WD
Subjects: Cross-Sectional Studies, Delivery of Health Care organization & administration, Female, Humans, Leadership, Male, Netherlands, Hospital Administration, Organizational Innovation, Total Quality Management
Abstract: Purpose - Lean healthcare is used in a growing number of hospitals to increase efficiency and quality of care. However, healthcare organizations encounter problems with the implementation of change initiatives due to an implementation gap: the gap between strategy and execution. From a change management perspective, the purpose of this paper is to increase scientific knowledge regarding factors that diminish the implementation gap and make the transition from the "toolbox lean" toward an actual transformation to lean healthcare. Design/methodology/approach - A cross-sectional study was executed in an operating theatre of a Dutch University Medical Centre. Transformational leadership was expected to ensure the required top-down commitment, whereas team leadership creates the required active, bottom-up behavior of employees. Furthermore, professional and functional silos and a hierarchical structure were expected to impede the workforce flexibility in adapting organizational elements and optimize the entire process flow. Findings - The correlation and regression analyses showed positive relations between the transformational leadership and team leadership styles and lean healthcare implementation. The results also indicated a strong relation between workforce flexibility and the implementation of lean healthcare. Originality/value - With the use of a recently developed change management model, the Change Competence Model, the authors suggest leadership and workforce flexibility to be part of an organization's change capacity as crucial success factor for a sustainable transformation to lean healthcare.
Published: 2016
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33. Mosquito salivary allergen Aed a 3: cloning, comprehensive molecular analysis, and clinical evaluation.

Author: Peng Z, Xu WW, Sham Y, Lam H, Sun D, Cheng L, Rasic NF, Guan Q, James AA, and Simons FE
Subjects: Adult, Aedes, Allergens chemistry, Amino Acid Sequence, Animals, Cloning, Molecular, DNA, Complementary, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoglobulin E immunology, Insect Bites and Stings diagnosis, Insect Bites and Stings immunology, Insect Proteins chemistry, Models, Molecular, Protein Binding, Protein Conformation, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins immunology, Salivary Proteins and Peptides chemistry, Sensitivity and Specificity, Sequence Analysis, DNA, Skin Tests, Allergens genetics, Allergens immunology, Insect Proteins genetics, Insect Proteins immunology, Salivary Proteins and Peptides genetics, Salivary Proteins and Peptides immunology
Abstract: Background: Allergic reactions to mosquito bites are an increasing clinical concern. Due to the lack of availability of mosquito salivary allergens, they are underdiagnosed. Here, we reported a newly cloned mosquito Aedes (Ae.) aegypti salivary allergen., Methods: A cDNA encoding a 30-kDa Ae. aegypti salivary protein, designated Aed a 3, was isolated from an expression library. The full-length cDNA was cloned into a baculovirus expression vector, and recombinant Aed a 3 (rAed a 3) was expressed, purified, and characterized. Skin prick tests with purified rAed a 3 and Ae. aegypti bite tests were performed in 43 volunteers. Serum rAed a 3-specific IgE levels were measured in 28 volunteers., Results: The primary nucleotide sequence, deduced amino acid sequence, and IgE-binding sites of Aed a 3 were identified. rAed a 3-selected antibodies recognized a 30-kDa Ae. aegypti saliva protein. rAed a 3 bound IgE in mosquito-allergic volunteers and the binding could be inhibited by the addition of natural mosquito extract dose dependently. Immediate skin test reactions to rAed a 3 correlated significantly with mosquito bite-induced reactions. Of the bite test-positive volunteers, 32% had a positive rAed a 3 skin test and 46% had specific IgE. No bite test-negative volunteers reacted to rAed a 3 in either the skin tests or the IgE assays, confirming the specificity of the assay., Conclusions: Aed a 3 that corresponds to the Aegyptin protein is a major mosquito salivary allergen. Its recombinant form has biological activity and is suitable for use in skin tests and specific IgE assays in mosquito-allergic individuals., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2016
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34. rAed a 4: A New 67-kDa Aedes aegypti Mosquito Salivary Allergen for the Diagnosis of Mosquito Allergy.

Author: Peng Z, Caihe L, Beckett AN, Guan Q, James AA, and Simons FE
Subjects: Animals, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin E blood, Immunoglobulin E immunology, Immunoglobulin G immunology, Insect Proteins immunology, Insect Proteins isolation & purification, Recombinant Proteins immunology, Salivary Proteins and Peptides immunology, Salivary Proteins and Peptides isolation & purification, Skin Tests, Aedes immunology, Allergens immunology, Hypersensitivity diagnosis, Hypersensitivity immunology, Insect Bites and Stings diagnosis, Insect Bites and Stings immunology
Abstract: Background: Accurate diagnosis of mosquito allergy has been hampered by the laborious task of obtaining mosquito salivary allergens. We have previously studied 3 recombinant (r) Aedes aegypti mosquito salivary allergens: rAed a 1, rAed a 2 and rAed a 3. Here, we report the expression, purification, identification and evaluation of rAed a 4, a 67-kDa α-glucosidase., Methods: rAed a 4 was expressed using a baculovirus/insect cell system, purified by a combination of anion- and cation-exchange chromatography, and identified by immunoblotting. A. aegypti saliva extract was prepared in our laboratory. An indirect enzyme-linked immunosorbent assay (ELISA) was developed to measure rAed a 4-specific immunoglobulin E (IgE) and IgG antibodies in sera from 13 individuals with a positive mosquito-bite test from a laboratory-reared mosquito. Sera from 18 individuals with a negative bite test served as controls., Results: Purified rAed a 4 bound to the IgE in mosquito-allergic sera, as detected by ELISA and immunoblotting. The binding of rAed a 4 to IgE could be inhibited in a dose-dependent manner by the addition of an A. aegypti extract. Mosquito-allergic individuals had significantly higher mean levels of rAed a 4-specific IgE and IgG than controls. Using the mean of the controls ± 2 SD as a cut-off level, 46% of the 13 allergic individuals had a positive IgE, while none of the controls was positive (p < 0.001)., Conclusions: Aed a 4 is a major allergen in mosquito saliva. Its recombinant form has the hydrolase function and can be used for the diagnosis of mosquito allergy., (© 2016 S. Karger AG, Basel.)
Published: 2016
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35. Epinephrine doses delivered from auto-injectors stored at excessively high temperatures.

Author: Rachid O, Simons FE, Rawas-Qalaji M, Lewis S, and Simons KJ
Subjects: Anaphylaxis drug therapy, Drug Stability, Drug Storage, Epinephrine therapeutic use, Humans, Pharmaceutical Solutions administration & dosage, Pharmaceutical Solutions therapeutic use, Epinephrine administration & dosage, Hot Temperature adverse effects, Injections instrumentation
Abstract: Context: Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25 °C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures., Objective: We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70 °C., Methods: Twenty-five in-date EAIs were stored constantly or cyclically at 70 °C (excessive heat) or 25 °C (controls) for 5 d or 10 d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV., Results: Control EAIs ejected a volume of 0.300 ± 0.006 mL containing 103.7 ± 3.3% of labeled dose (LD). After 5 d or 10 d of constant storage at 70 °C and activation at 70 °C, EAIs ejected a volume of 0.367 ± 0.008 mL containing 96.8 ± 3.8% LD and 0.373 ± 0.007 mL containing 77.7 ± 3.3% LD, respectively. After 5 d of cyclic storage at 70 °C and cooling to 25 °C before activation, EAIs ejected a volume of 0.311 ± 0.008 mL containing 87.2 ± 1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine., Conclusion: EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.
Published: 2016
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36. MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Author: Bousquet J, Schunemann HJ, Fonseca J, Samolinski B, Bachert C, Canonica GW, Casale T, Cruz AA, Demoly P, Hellings P, Valiulis A, Wickman M, Zuberbier T, Bosnic-Anticevitch S, Bedbrook A, Bergmann KC, Caimmi D, Dahl R, Fokkens WJ, Grisle I, Lodrup Carlsen K, Mullol J, Muraro A, Palkonen S, Papadopoulos N, Passalacqua G, Ryan D, Valovirta E, Yorgancioglu A, Aberer W, Agache I, Adachi M, Akdis CA, Akdis M, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielhe S, Arshad H, Baiardini I, Baigenzhin AK, Barbara C, Bateman ED, Beghé B, Bel EH, Ben Kheder A, Bennoor KS, Benson M, Bewick M, Bieber T, Bindslev-Jensen C, Bjermer L, Blain H, Boner AL, Boulet LP, Bonini M, Bonini S, Bosse I, Bourret R, Bousquet PJ, Braido F, Briggs AH, Brightling CE, Brozek J, Buhl R, Burney PG, Bush A, Caballero-Fonseca F, Calderon MA, Camargos PA, Camuzat T, Carlsen KH, Carr W, Cepeda Sarabia AM, Chavannes NH, Chatzi L, Chen YZ, Chiron R, Chkhartishvili E, Chuchalin AG, Ciprandi G, Cirule I, Correia de Sousa J, Cox L, Crooks G, Costa DJ, Custovic A, Dahlen SE, Darsow U, De Carlo G, De Blay F, Dedeu T, Deleanu D, Denburg JA, Devillier P, Didier A, Dinh-Xuan AT, Dokic D, Douagui H, Dray G, Dubakiene R, Durham SR, Dykewicz MS, El-Gamal Y, Emuzyte R, Fink Wagner A, Fletcher M, Fiocchi A, Forastiere F, Gamkrelidze A, Gemicioğlu B, Gereda JE, González Diaz S, Gotua M, Grouse L, Guzmán MA, Haahtela T, Hellquist-Dahl B, Heinrich J, Horak F, Hourihane JO, Howarth P, Humbert M, Hyland ME, Ivancevich JC, Jares EJ, Johnston SL, Joos G, Jonquet O, Jung KS, Just J, Kaidashev I, Kalayci O, Kalyoncu AF, Keil T, Keith PK, Khaltaev N, Klimek L, Koffi N'Goran B, Kolek V, Koppelman GH, Kowalski ML, Kull I, Kuna P, Kvedariene V, Lambrecht B, Lau S, Larenas-Linnemann D, Laune D, Le LT, Lieberman P, Lipworth B, Li J, Louis R, Magard Y, Magnan A, Mahboub B, Majer I, Makela MJ, Manning P, De Manuel Keenoy E, Marshall GD, Masjedi MR, Maurer M, Mavale-Manuel S, Melén E, Melo-Gomes E, Meltzer EO, Merk H, Miculinic N, Mihaltan F, Milenkovic B, Mohammad Y, Molimard M, Momas I, Montilla-Santana A, Morais-Almeida M, Mösges R, Namazova-Baranova L, Naclerio R, Neou A, Neffen H, Nekam K, Niggemann B, Nyembue TD, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Ouedraogo S, Paggiaro P, Pali-Schöll I, Palmer S, Panzner P, Papi A, Park HS, Pavord I, Pawankar R, Pfaar O, Picard R, Pigearias B, Pin I, Plavec D, Pohl W, Popov TA, Portejoie F, Postma D, Potter P, Price D, Rabe KF, Raciborski F, Radier Pontal F, Repka-Ramirez S, Robalo-Cordeiro C, Rolland C, Rosado-Pinto J, Reitamo S, Rodenas F, Roman Rodriguez M, Romano A, Rosario N, Rosenwasser L, Rottem M, Sanchez-Borges M, Scadding GK, Serrano E, Schmid-Grendelmeier P, Sheikh A, Simons FE, Sisul JC, Skrindo I, Smit HA, Solé D, Sooronbaev T, Spranger O, Stelmach R, Strandberg T, Sunyer J, Thijs C, Todo-Bom A, Triggiani M, Valenta R, Valero AL, van Hage M, Vandenplas O, Vezzani G, Vichyanond P, Viegi G, Wagenmann M, Walker S, Wang DY, Wahn U, Williams DM, Wright J, Yawn BP, Yiallouros PK, Yusuf OM, Zar HJ, Zernotti ME, Zhang L, Zhong N, Zidarn M, and Mercier J
Subjects: Allergens immunology, Biomarkers, Clinical Decision-Making methods, Clinical Trials as Topic, Comorbidity, Disease Management, Health Planning, Health Policy, Humans, Medical Informatics methods, Practice Guidelines as Topic, Reproducibility of Results, Rhinitis, Allergic epidemiology, Rhinitis, Allergic immunology, Rhinitis, Allergic prevention & control, Web Browser, Rhinitis, Allergic diagnosis, Rhinitis, Allergic therapy
Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2015
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37. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines.

Author: Simons FE, Ebisawa M, Sanchez-Borges M, Thong BY, Worm M, Tanno LK, Lockey RF, El-Gamal YM, Brown SG, Park HS, and Sheikh A
Abstract: The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research.
Published: 2015
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38. Sublingual Diffusion of Epinephrine Microcrystals from Rapidly Disintegrating Tablets for the Potential First-Aid Treatment of Anaphylaxis: In Vitro and Ex Vivo Study.

Author: Rawas-Qalaji MM, Werdy S, Rachid O, Simons FE, and Simons KJ
Subjects: Administration, Sublingual, Anti-Allergic Agents administration & dosage, Calorimetry, Differential Scanning, Crystallization, Diffusion, Drug Compounding, Epinephrine administration & dosage, Humans, Kinetics, Microscopy, Electron, Scanning, Particle Size, Solubility, Spectroscopy, Fourier Transform Infrared, Technology, Pharmaceutical methods, Anaphylaxis drug therapy, Anti-Allergic Agents chemistry, Epinephrine chemistry, First Aid methods
Abstract: For the first-aid treatment of anaphylaxis, epinephrine (Epi) 0.3 mg intramuscular (IM) injection in the thigh is the drug of choice. Epi auto-injectors are widely recommended for anaphylaxis treatment in community settings but not necessarily carried or used as prescribed when anaphylaxis occurs. We therefore developed rapidly disintegrating sublingual tablets (RDSTs) as an alternative noninvasive dosage form. Our objective in this study was to evaluate the effect of reducing Epi particle size on its in vitro and ex vivo diffusion, with the goal of enhancing Epi sublingual absorption from Epi RDSTs. Epi particle size was reduced by top-bottom technique using a microfluidizer for one pass at 30,000 Psi. The micronized Epi crystals (Epi-MC) were characterized using Zetasizer, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Epi RDSTs were formulated and manufactured using our previously developed method. In vitro and ex vivo diffusion of Epi 10, 20, and 40 mg RDSTs and Epi-MC 10 and 20 mg RDSTs (n = 4) were evaluated using Franz cells. Epi 10 mg solution was used as a control. Mean (±standard deviation (SD)) Epi particle size was successfully reduced from 131.8 ± 10.5 to 2.5 ± 0.4 μm. Cumulative Epi diffused and influx from 40 mg Epi RDSTs and 20 mg Epi-MC RDSTs were not significantly different from each other in vitro and ex vivo (p > 0.05). Also, Epi permeability from 20 mg Epi-MC RDSTs was significantly higher than from the rest (p < 0.05). Epi-MC RDSTs improved Epi diffusion twofold and might have the potential to reduce the Epi dose needed in RDSTs by 50%.
Published: 2015
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39. H1-antihistamines for primary mast cell activation syndromes: a systematic review.

Author: Nurmatov UB, Rhatigan E, Simons FE, and Sheikh A
Subjects: Disease Management, Histamine H1 Antagonists pharmacology, Humans, Mast Cells drug effects, Mast Cells immunology, Mast Cells metabolism, Mastocytosis diagnosis, Randomized Controlled Trials as Topic, Syndrome, Treatment Outcome, Histamine H1 Antagonists therapeutic use, Mastocytosis drug therapy
Abstract: Background: Primary mast cell activation syndromes (MCAS) are a group of disorders presenting with symptoms of mast cell mediator release., Objectives: To assess the effectiveness and safety of orally administered H1 -antihistamines in the treatment of primary MCAS compared with placebo and other pharmacologic treatments., Methods: We systematically searched five databases and three trial repositories and contacted an international panel of experts to identify published and unpublished trials., Results: A total of 36 potentially relevant studies were identified. Of these, five crossover trials, enrolling a total of 71 patients (63 adults), met the eligibility criteria. All five of these studies were judged to be at moderate or high risk of bias. Two studies compared an H1 -antihistamine with placebo, two compared two different H1 -antihistamines, and one study compared H1 - and H2 -antihistamines with oral cromolyn sodium. Four of the five randomized controlled trials were historic (reported from 1983-1993), small (enrolling 8-15 patients), and used agents and/or dosing regimens that are now less commonly used in clinical practice (i.e. azelastine, chlorpheniramine, hydroxyzine, and ketotifen). The fifth trial, which enrolled 33 adults with cutaneous and systemic mastocytosis found 4 weeks of treatment with the second-generation H1 -antihistamine rupatadine, compared with placebo, resulted in significant improvements in quality of life, symptom control (itching, wheals and flares, flushing, tachycardia, and headache, but not gastrointestinal symptoms), and reduction in itching and whealing after standardized skin provocation to elicit Darier's sign., Conclusions: There is an urgent need for large, well-designed, double-blind, placebo-controlled randomized trials investigating the effectiveness, cost-effectiveness, and safety of second-generation H1 -antihistamines in treatment of primary MCAS., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2015
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40. Anaphylaxis and cardiovascular disease: therapeutic dilemmas.

Author: Lieberman P and Simons FE
Subjects: Animals, Humans, Mast Cells pathology, Myocardial Contraction immunology, Myocardium pathology, Anaphylaxis etiology, Anaphylaxis immunology, Anaphylaxis pathology, Anaphylaxis therapy, Cardiovascular Diseases complications, Cardiovascular Diseases immunology, Cardiovascular Diseases pathology, Cardiovascular Diseases therapy, Mast Cells immunology, Myocardium immunology
Abstract: Cardiovascular disease (CVD) increases the risk of severe or fatal anaphylaxis, and some medications for CVD treatment can exacerbate anaphylaxis. The aim of this article is to review the effect of anaphylaxis on the heart, the potential impact of medications for CVD on anaphylaxis and anaphylaxis treatment, and the cardiovascular effects of epinephrine. The therapeutic dilemmas arising from these issues are also discussed and management strategies proposed. PubMed searches were performed for the years 1990-2014 inclusive, using terms such as angiotensin-converting enzyme (ACE) inhibitors, adrenaline, allergic myocardial infarction, anaphylaxis, angiotensin-receptor blockers (ARBs), beta-adrenergic blockers, epinephrine, and Kounis syndrome. Literature analysis indicated that: cardiac mast cells are key constituents of atherosclerotic plaques; mast cell mediators play an important role in acute coronary syndrome (ACS); patients with CVD are at increased risk of developing severe or fatal anaphylaxis; and medications for CVD treatment, including beta-adrenergic blockers and ACE inhibitors, potentially exacerbate anaphylaxis or make it more difficult to treat. Epinephrine increases myocardial contractility, decreases the duration of systole relative to diastole, and enhances coronary blood flow. Its transient adverse effects include pallor, tremor, anxiety, and palpitations. Serious adverse effects (including ventricular arrhythmias and hypertension) are rare, and are significantly more likely after intravenous injection than after intramuscular injection. Epinephrine is life-saving in anaphylaxis; second-line medications (including antihistamines and glucocorticoids) are not. In CVD patients (especially those with ACS), the decision to administer epinephrine for anaphylaxis can be difficult, and its benefits and potential harms need to be carefully considered. Concerns about potential adverse effects need to be weighed against concerns about possible death from untreated anaphylaxis, but there is no absolute contraindication to epinephrine injection in anaphylaxis., (© 2015 John Wiley & Sons Ltd.)
Published: 2015
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41. Drug-device combination products in the twenty-first century: epinephrine auto-injector development using human factors engineering.

Author: Edwards ES, Edwards ET, Simons FE, and North R
Subjects: Epinephrine adverse effects, Humans, Injections, Reproducibility of Results, Anaphylaxis drug therapy, Epinephrine administration & dosage, Ergonomics
Abstract: Introduction: The systematic application of human factors engineering (HFE) principles to the development of drug-device combination products, including epinephrine auto-injectors (EAIs), has the potential to improve the effectiveness and safety of drug administration., Areas Covered: A PubMed search was performed to assess the role of HFE in the development of drug-device combination products. The following keywords were used in different combinations: 'human factors engineering,' 'human factors,' 'medical products,' 'epinephrine/adrenaline auto-injector,' 'healthcare' and 'patient safety.' This review provides a summary of HFE principles and their application to the development of drug-device combination products as advised by the US FDA. It also describes the HFE process that was applied to the development of Auvi-Q, a novel EAI, highlighting specific steps that occurred during the product-development program., Expert Opinion: For drug-device combination products, device labeling and usability are critical and have the potential to impact clinical outcomes. Application of HFE principles to the development of drug-delivery devices has the potential to improve product quality and reliability, reduce risk and improve patient safety when applied early in the development process. Additional clinical and real-world studies will confirm whether the application of HFE has helped to develop an EAI that better meets the needs of patients at risk of anaphylaxis.
Published: 2015
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42. Anaphylaxis: Unique aspects of clinical diagnosis and management in infants (birth to age 2 years).

Author: Simons FE and Sampson HA
Subjects: Age Factors, Anaphylaxis etiology, Anaphylaxis prevention & control, Child, Preschool, Disease Management, Humans, Infant, Infant, Newborn, Risk Factors, Anaphylaxis diagnosis, Anaphylaxis therapy
Abstract: In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein-induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
Published: 2015
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43. Epinephrine doses contained in outdated epinephrine auto-injectors collected in a Florida allergy practice.

Author: Rachid O, Simons FE, Wein MB, Rawas-Qalaji M, and Simons KJ
Subjects: Bronchodilator Agents administration & dosage, Drug Dosage Calculations, Epinephrine administration & dosage, Florida, Humans, Time Factors, Anaphylaxis drug therapy, Bronchodilator Agents analysis, Drug Storage, Epinephrine analysis, Medication Errors prevention & control
Published: 2015
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44. Epinephrine autoinjectors: does freezing or refrigeration affect epinephrine dose delivery and enantiomeric purity?

Author: Rachid O, Simons FE, Rawas-Qalaji M, Lewis S, and Simons KJ
Subjects: Drug Stability, Epinephrine administration & dosage, Injections, Stereoisomerism, Cold Temperature, Drug Delivery Systems, Epinephrine chemistry
Published: 2015
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45. Anaphylaxis in America: A national physician survey.

Author: Altman AM, Camargo CA Jr, Simons FE, Lieberman P, Sampson HA, Schwartz LB, Zitt FM, Collins C, Tringale M, Wilkinson M, and Wood RA
Subjects: Adult, Anaphylaxis drug therapy, Anaphylaxis immunology, Anaphylaxis physiopathology, Child, Food Hypersensitivity drug therapy, Food Hypersensitivity immunology, Food Hypersensitivity physiopathology, Health Knowledge, Attitudes, Practice, Humans, Physicians, Anaphylaxis diagnosis, Clinical Competence statistics & numerical data, Epinephrine therapeutic use, Food Hypersensitivity diagnosis, Health Care Surveys statistics & numerical data
Published: 2015
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46. Insights and advances in chronic urticaria: a Canadian perspective.

Author: Sussman G, Hébert J, Gulliver W, Lynde C, Waserman S, Kanani A, Ben-Shoshan M, Horemans S, Barron C, Betschel S, Yang WH, Dutz J, Shear N, Lacuesta G, Vadas P, Kobayashi K, Lima H, and Simons FE
Abstract: In the past few years there have been significant advances which have changed the face of chronic urticaria. In this review, we aim to update physicians about clinically relevant advances in the classification, diagnosis and management of chronic urticaria that have occurred in recent years. These include clarification of the terminology used to describe and classify urticaria. We also detail the development and validation of instruments to assess urticaria and understand the impairment on quality-of-life and the morbidity caused by this disease. Additionally, the approach to management of chronic urticaria now focuses on evidence-based use of non-impairing, non-sedating H1-antihistamines given initially in standard doses and if this is not effective, in up to 4-fold doses. For urticaria refractory to H1-antihistamines, omalizumab treatment has emerged as an effective, safe option.
Published: 2015
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47. Update on rupatadine in the management of allergic disorders.

Author: Mullol J, Bousquet J, Bachert C, Canonica GW, Giménez-Arnau A, Kowalski ML, Simons FE, Maurer M, Ryan D, and Scadding G
Subjects: Cyproheptadine pharmacology, Cyproheptadine therapeutic use, Humans, Hypersensitivity diagnosis, Hypersensitivity etiology, Platelet Activating Factor pharmacology, Treatment Outcome, Cyproheptadine analogs & derivatives, Hypersensitivity drug therapy, Platelet Activating Factor therapeutic use
Abstract: In a review of rupatadine published in 2008, the primary focus was on its role as an antihistamine, with a thorough evaluation of its pharmacology and interaction with histamine H1 -receptors. At the time, however, evidence was already emerging of a broader mechanism of action for rupatadine involving other mediators implicated in the inflammatory cascade. Over the past few years, the role of platelet-activating factor (PAF) as a potent mediator involved in the hypersensitivity-type allergic reaction has gained greater recognition. Rupatadine has dual affinity for histamine H1 -receptors and PAF receptors. In view of the Allergic Rhinitis and its Impact on Asthma group's call for oral antihistamines to exhibit additive anti-allergic/anti-inflammatory properties, further exploration of rupatadine's anti-PAF effects was a logical step forward. New studies have demonstrated that rupatadine inhibits PAF effects in nasal airways and produces a greater reduction in nasal symptoms than levocetirizine. A meta-analysis involving more than 2500 patients has consolidated the clinical evidence for rupatadine in allergic rhinoconjunctivitis in adults and children (level of evidence Ia, recommendation A). Other recent advances include observational studies of rupatadine in everyday clinical practice situations and approval of a new formulation (1 mg/ml oral solution) for use in children. In this reappraisal, we revisit some key properties and pivotal clinical studies of rupatadine and examine new clinical data in more detail including studies that measured health-related quality of life and studies that investigated the efficacy and safety of rupatadine in other indications such as acquired cold urticaria, mosquito bite allergy and mastocytosis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2015
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48. Adrenaline (epinephrine) microcrystal sublingual tablet formulation: enhanced absorption in a preclinical model.

Author: Rawas-Qalaji M, Rachid O, Mendez BA, Losada A, Simons FE, and Simons KJ
Subjects: Administration, Sublingual, Anaphylaxis drug therapy, Animals, Area Under Curve, Chemistry, Pharmaceutical, Epinephrine therapeutic use, Female, Injections, Intramuscular, Metabolic Clearance Rate, Particle Size, Prospective Studies, Rabbits, Epinephrine administration & dosage, Epinephrine pharmacokinetics, Tablets chemistry
Abstract: Objectives: For anaphylaxis treatment in community settings, adrenaline (epinephrine) administration using an auto-injector in the thigh is universally recommended. Despite this, many people at risk of anaphylaxis in community settings do not carry their prescribed auto-injectors consistently and hesitate to use them when anaphylaxis occurs.The objective of this research was to study the effect of a substantial reduction in adrenaline (Epi) particle size to a few micrometres (Epi microcrystals (Epi-MC)) on enhancing adrenaline dissolution and increasing the rate and extent of sublingual absorption from a previously developed rapidly disintegrating sublingual tablet (RDST) formulation in a validated preclinical model., Methods: The in-vivo absorption of Epi-MC 20 mg RDSTs and Epi 40 mg RDSTs was evaluated in rabbits. Epi 0.3 mg intramuscular (IM) injection in the thigh and placebo RDSTs were used as positive and negative controls, respectively., Key Findings: Epimean (standard deviation) area under the plasma concentration vs time curves up to 60 min and Cmax from Epi-MC 20 mg and Epi 40 mg RDSTs did not differ significantly (P > 0.05) from Epi 0.3 mg IM injection. After adrenaline, regardless of route of administration, pharmacokinetic parameters were significantly higher (P < 0.05) than after placebo RDSTs administration (reflecting endogenous adrenaline levels)., Conclusion: Epi-MC RDSTs facilitated a twofold increase in Epi absorption and a 50% reduction in the sublingual dose. This novel sublingual tablet formulation is potentially useful for the first-aid treatment of anaphylaxis in community settings., (© 2014 Royal Pharmaceutical Society.)
Published: 2015
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49. Patient safety in the operating theatre: how A3 thinking can help reduce door movement.

Author: Simons FE, Aij KH, Widdershoven GA, and Visse M
Subjects: Academic Medical Centers statistics & numerical data, Efficiency, Organizational, Humans, Netherlands, Operating Rooms statistics & numerical data, Quality Improvement statistics & numerical data, Academic Medical Centers organization & administration, Operating Rooms organization & administration, Patient Safety, Quality Improvement organization & administration, Surgical Wound Infection prevention & control
Abstract: Issue: Research has often stressed the significance of reducing door movement during surgery for preventing surgical site infections. This study investigated the possible effect of a lean A3 intervention on the reduction of door movement during surgery in a university medical center in the Netherlands., Initial Assessment: A digital counter recorded door movement during 8009 surgical procedures during 8 months. The number of door movements per surgical procedure ranged from 0 to 555, with a mean of 24 door movements per hour across 26 specialisms., Choice of Solution: We aimed to reduce door movement in one operating room for orthopedic surgery by a lean A3 intervention. This intervention was executed by means of an A3 report that promotes structured problem solving based on a Plan-Do-Check-Act cycle., Implementation: The steps of the A3 report was followed and completed one-by-one by a multidisciplinary team. The effect of the changes was monitored over the course of 12 months., Evaluation: The use of a lean A3 intervention resulted in a sustainable decrease of door movements by 78%, from a mean of 24 to a mean of 4 door movements per hour during orthopedic surgery at one OR., Lessons Learned: This paper shows the relevance of and the possibility for a reduction of door movement during surgery by lean management methods in general and an A3 intervention in particular. This intervention stimulated dialogue and encouraged knowledge-sharing and collaboration between specialized healthcare professionals and this resulted in a thorough root-cause analysis that provided synergy in the countermeasures-with, according to respondents, a sustainable result., (© The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.)
Published: 2014
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50. Methods report on the development of the 2013 revision and update of the EAACI/GA2 LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria.

Author: Zuberbier T, Aberer W, Asero R, Bindslev-Jensen C, Brzoza Z, Canonica GW, Church MK, Ensina LF, Giménez-Arnau A, Godse K, Gonçalo M, Grattan C, Hebert J, Hide M, Kaplan A, Kapp A, Abdul Latiff AH, Mathelier-Fusade P, Metz M, Saini SS, Sánchez-Borges M, Schmid-Grendelmeier P, Simons FE, Staubach P, Sussman G, Toubi E, Vena GA, Wedi B, Zhu XJ, Nast A, and Maurer M
Subjects: Evidence-Based Medicine, Humans, Urticaria classification, Urticaria diagnosis, Urticaria therapy
Abstract: This methods report describes the process of guideline development in detail. It is the result of a systematic literature review using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Network (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS) and is published in Allergy 2014; 69:868-887., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2014
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