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1. The triple radiologic asthma phenotype is associated with worse disease control

Author: Rory Chan, MBChB, PhD, Chary Duraikannu, FRCR, Mohamed Jaushal Thouseef, FRCR, and Brian Lipworth, MD
Subjects: Asthma, symptom control, imaging, computed tomography, bronchial wall thickness, mucus plug, Immunologic diseases. Allergy, RC581-607
Abstract: Background: Efforts have been made to combine radiographic biomarkers such as bronchiectasis or bronchial wall thickness (BWT) for the purpose of identifying asthma subphenotypes and their clinical implications. Objective: Our aim was to assess whether a composite triple radiologic phenotype measured by high-resolution computed tomography comprising BWT, mucus plug score (MPS), and mediastinal lymph node (MLN) size might provide a better insight into subphenotypes in persistent asthma. Methods: A total of 112 patients with moderate-to-severe asthma were included in this retrospective observational study. A binary method was used to classify patients according to median values for the following: a pooled mediastinal lymph node size of 3.6 mm or more; a BWT as a pooled wall area of at least 50% of the total airway area; and a mucus plug score of 1 or higher, with a mucus plug considered positive if complete bronchial obstruction was imaged more than 2 cm from a pleural surface. Results: Patients with the triple imaging phenotype exhibited significantly worse Asthma Control Questionnaire scores, with their scores exceeding minimal clinical important difference, a higher prevalence of concomitant chronic rhinosinusitis with nasal polyps, and a greater total IgE level. Conclusion: We have demonstrated an association between poorer symptom control and the triple radiologic asthma phenotype.
Published: 2024
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2. Patient-Reported Outcomes with Benralizumab in Patients with Severe Eosinophilic Asthma and Severe Chronic Rhinosinusitis with Nasal Polyps

Author: Rory Chan, Kirsten Stewart, Rasads Misirovs, and Brian Lipworth
Subjects: benralizumab, asthma, nasal polyps, eosinophils, patient-reported outcomes, Otorhinolaryngology, RF1-547
Abstract: Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) and severe eosinophilic asthma (SEA) are common comorbidities characterised by type 2 inflammation associated with increased expression of interleukin 5. Methods: Eight patients with SEA and severe CRSwNP attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT number 2019-003763-22). Following an initial 4-week run-in period (baseline) when patients took their usual inhaled and intranasal corticosteroid treatment for SEA and CRSwNP, they all received subcutaneous benralizumab 30 mg q4w for 12 weeks. Results: Following 12 weeks of benralizumab, no significant differences were detected in nasal global symptom visual analogue score (VAS), hyposmia VAS, total nasal symptom score, or peak nasal inspiratory flow. In contrast, Asthma Control Questionnaire significantly improved along with near-complete depletion of peripheral blood eosinophils by 99%, while eosinophil-derived neurotoxin fell by 72%. Conclusions: Greater improvements in patient-reported outcomes related to asthma were observed than with CRSwNP in response to benralizumab.
Published: 2023
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3. Medium-term repeatability for airwave oscillometry in patients with severe asthma taking benralizumab

Author: Rory Chan, MBChB, PhD and Brian Lipworth, MD
Subjects: Benralizumab, asthma, airway oscillometry, repeatability, Immunologic diseases. Allergy, RC581-607
Abstract: Background: The effort-independent tidal breathing test used by oscillometry presents a viable alternative for following up patients whose condition is stable while they are receiving biologic therapy. Objective: We aimed to determine intrasession and intersession repeatability values for airwave oscillometry (AOS) and spirometry in patients who were already taking benralizumab. Methods: In all, 21 patients with severe eosinophilic asthma attended the Scottish Centre for Respiratory Research as part of a clinical trial (EudraCT identification number 2019-003763-22). Paired AOS and spirometry values were obtained at 3 separate visits (baseline and days 28 and 56) with no change in asthma therapy. Results: Intrasession agreement between repeated measurements for AOS and spirometry was excellent (intraclass correlation coefficient ≥ 0.90) at all 3 visits. Intersession agreement was also excellent (intraclass correlation coefficient ≥ 0.80). Conclusion: In this study we report medium-term intrasession and intersession repeatability values for airwave oscillometry and spirometry in a cohort of severely asthmatic patients receiving benralizumab therapy. Oscillometry can be used to follow up patients with asthma who are taking biologics.
Published: 2023
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4. Real‐world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities

Author: Bernardo Sousa‐Pinto, Aram Anto, Markus Berger, Stephanie Dramburg, Oliver Pfaar, Ludger Klimek, Marek Jutel, Wienczyslawa Czarlewski, Anna Bedbrook, Arunas Valiulis, Ioana Agache, Rita Amaral, Ignacio J. Ansotegui, Katharina Bastl, Uwe Berger, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, Fulvio Braido, Luisa Brussino, Victoria Cardona, Thomas Casale, G. Walter Canonica, Lorenzo Cecchi, Denis Charpin, Tomás Chivato, Derek K. Chu, Cemal Cingi, Elisio M. Costa, Alvaro A. Cruz, Philippe Devillier, Stephen R. Durham, Motohiro Ebisawa, Alessandro Fiocchi, Wytske J. Fokkens, Bilun Gemicioğlu, Maia Gotua, Maria‐Antonieta Guzmán, Tari Haahtela, Juan Carlos Ivancevich, Piotr Kuna, Igor Kaidashev, Musa Khaitov, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Brian Lipworth, Daniel Laune, Paolo M. Matricardi, Mario Morais‐Almeida, Joaquim Mullol, Robert Naclerio, Hugo Neffen, Kristoff Nekam, Marek Niedoszytko, Yoshitaka Okamoto, Nikolaos G. Papadopoulos, Hae‐Sim Park, Giovanni Passalacqua, Vincenzo Patella, Simone Pelosi, Nhân Pham‐Thi, Ted A. Popov, Frederico S. Regateiro, Sietze Reitsma, Monica Rodriguez‐Gonzales, Nelson Rosario, Philip W. Rouadi, Boleslaw Samolinski, Ana Sá‐Sousa, Joaquin Sastre, Aziz Sheikh, Charlotte Suppli Ulrik, Luis Taborda‐Barata, Ana Todo‐Bom, Peter Valentin Tomazic, Sanna Toppila‐Salmi, Salvatore Tripodi, Ioanna Tsiligianni, Erkka Valovirta, Maria Teresa Ventura, Antonio A. Valero, Rafael José Vieira, Dana Wallace, Susan Waserman, Sian Williams, Arzu Yorgancioglu, Luo Zhang, Mihaela Zidarn, Jaron Zuberbier, Heidi Olze, Josep M. Antó, Torsten Zuberbier, João A. Fonseca, and Jean Bousquet
Subjects: allergic rhinitis, app, chronic rhinosinusitis, mHealth, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.
Published: 2022
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5. Low-Grade B Cell Lymphoproliferative Disorder Masquerading as Chronic Rhinosinusitis

Author: Rory Chan, Chris RuiWen Kuo, and Brian Lipworth
Subjects: chronic rhinosinusitis, B-cell lymphoproliferative disorder, Otorhinolaryngology, RF1-547
Abstract: Chronic rhinosinusitis (CRS) is one of the most common persistent disorders of the developed world, requiring input from various specialists including primary care physicians, otolaryngologists, respiratory physicians, and allergologists. B-cell lymphoproliferative disorders (BLPDs) are a heterogenous group of malignant conditions defined by an accumulation of mature B lymphocytes in the bone marrow, blood, and lymphoid tissues. We present a case report of an elderly man with rhinosinusitis-like symptoms and atypical features prompting further investigations that culminated in a diagnosis of BLPD.
Published: 2021
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6. Allergen immunotherapy in MASK‐air users in real‐life: Results of a Bayesian mixed‐effects model

Author: Bernardo Sousa‐Pinto, Luís Filipe Azevedo, Ana Sá‐Sousa, Rafael José Vieira, Rita Amaral, Ludger Klimek, Wienczyslawa Czarlewski, Josep M. Anto, Anna Bedbrook, Violeta Kvedariene, Maria Teresa Ventura, Ignacio J. Ansotegui, Karl‐Christian Bergmann, Luisa Brussino, G. Walter Canonica, Victoria Cardona, Pedro Carreiro‐Martins, Thomas Casale, Lorenzo Cecchi, Tomás Chivato, Derek K. Chu, Cemal Cingi, Elisio M. Costa, Alvaro A. Cruz, Giulia De Feo, Philippe Devillier, Wytske J. Fokkens, Mina Gaga, Bilun Gemicioğlu, Tari Haahtela, Juan Carlos Ivancevich, Zhanat Ispayeva, Marek Jutel, Piotr Kuna, Igor Kaidashev, Helga Kraxner, Désirée E. Larenas‐Linnemann, Daniel Laune, Brian Lipworth, Renaud Louis, Michaël Makris, Riccardo Monti, Mario Morais‐Almeida, Ralph Mösges, Joaquim Mullol, Mikaëla Odemyr, Yoshitaka Okamoto, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Milan Sova, Ana Todo‐Bom, Luis Taborda‐Barata, Peter Valentin Tomazic, Sanna Toppila‐Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, João Almeida Fonseca, Jean Bousquet, and Oliver Pfaar
Subjects: allergic rhinitis, immunotherapy, mobile health, patient‐reported outcomes, real‐life data analysis, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.
Published: 2022
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7. Does unified allergic airway disease impact on lung function and type 2 biomarkers?

Author: Chris RuiWen Kuo, Rory Chan, and Brian Lipworth
Subjects: Unified allergic airway disease, Asthma, Allergic rhinitis, Asthma control questionnaire, Fractional exhaled nitric oxide, Eosinophil, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract The concept of the unified allergic airway disease (UAD) recognises the association between allergic inflammation in the upper and lower airways. Patients with asthma and concomitant allergic rhinitis experience more asthma-related primary and secondary care visits. We therefore aimed to determine differences in asthma control (asthma control questionnaire ACQ-6), lung function (spirometry) and T2 biomarkers (FeNO and Eos) in relation to the presence of allergic rhinitis in patients with allergic asthma. Retrospectively, we evaluated a cohort of 60 consecutive patients with persistent asthma attending our research unit for screening into clinical trials. All included subjects were receiving inhaled corticosteroids (ICS) and had a positive skin prick test (SPT) to at least one common aeroallergen to fulfil the criterion of allergic asthma. Patients with UAD had a diagnosis of allergic asthma in addition to established concomitant allergic rhinitis. T2 biomarkers were significantly higher in patients with allergic rhinitis in contrast to those without. FEV1 % predicted and FEF25-75 % predicted were also significantly lower in patients with concomitant allergic rhinitis. However, there was no difference in ACQ-6 observed between groups. In summary, patients with allergic asthma, the presence of concomitant allergic rhinitis is associated with worse lung function and higher type 2 biomarkers.
Published: 2019
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8. Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases

Author: J. Jean Bousquet, Holger J. Schünemann, Alkis Togias, Marina Erhola, Peter W. Hellings, Torsten Zuberbier, Ioana Agache, Ignacio J. Ansotegui, Josep M. Anto, Claus Bachert, Sven Becker, Martin Bedolla-Barajas, Michael Bewick, Sinthia Bosnic-Anticevich, Isabelle Bosse, Louis P. Boulet, Jean Marc Bourrez, Guy Brusselle, Niels Chavannes, Elisio Costa, Alvaro A. Cruz, Wienczyslawa Czarlewski, Wytske J. Fokkens, Joao A. Fonseca, Mina Gaga, Tari Haahtela, Maddalena Illario, Ludger Klimek, Piotr Kuna, Violeta Kvedariene, L. T. T. Le, Desiree Larenas-Linnemann, Daniel Laune, Olga M. Lourenço, Enrica Menditto, Joaquin Mullol, Yashitaka Okamoto, Nikos Papadopoulos, Nhân Pham-Thi, Robert Picard, Hilary Pinnock, Nicolas Roche, Regina E. Roller-Wirnsberger, Christine Rolland, Boleslaw Samolinski, Aziz Sheikh, Sanna Toppila-Salmi, Ioanna Tsiligianni, Arunas Valiulis, Erkka Valovirta, Tuula Vasankari, Maria-Teresa Ventura, Samantha Walker, Sian Williams, Cezmi A. Akdis, Isabella Annesi-Maesano, Sylvie Arnavielhe, Xavier Basagana, Eric Bateman, Anna Bedbrook, K. S. Bennoor, Samuel Benveniste, Karl C. Bergmann, Slawomir Bialek, Nils Billo, Carsten Bindslev-Jensen, Leif Bjermer, Hubert Blain, Mateo Bonini, Philippe Bonniaud, Jacques Bouchard, Vitalis Briedis, Christofer E. Brightling, Jan Brozek, Roland Buhl, Roland Buonaiuto, Giorgo W. Canonica, Victoria Cardona, Ana M. Carriazo, Warner Carr, Christine Cartier, Thomas Casale, Lorenzo Cecchi, Alfonso M. Cepeda Sarabia, Eka Chkhartishvili, Derek K. Chu, Cemal Cingi, Elaine Colgan, Jaime Correia de Sousa, Anne Lise Courbis, Adnan Custovic, Biljana Cvetkosvki, Gennaro D’Amato, Jane da Silva, Carina Dantas, Dejand Dokic, Yves Dauvilliers, Antoni Dedeu, Giulia De Feo, Philippe Devillier, Stefania Di Capua, Marc Dykewickz, Ruta Dubakiene, Motohiro Ebisawa, Yaya El-Gamal, Esben Eller, Regina Emuzyte, John Farrell, Antjie Fink-Wagner, Alessandro Fiocchi, Jean F. Fontaine, Bilun Gemicioğlu, Peter Schmid-Grendelmeir, Amiran Gamkrelidze, Judith Garcia-Aymerich, Maximiliano Gomez, Sandra González Diaz, Maia Gotua, Nick A. Guldemond, Maria-Antonieta Guzmán, Jawad Hajjam, John O’B Hourihane, Marc Humbert, Guido Iaccarino, Despo Ierodiakonou, Juan C. Ivancevich, Guy Joos, Ki-Suck Jung, Marek Jutel, Igor Kaidashev, Omer Kalayci, Przemyslaw Kardas, Thomas Keil, Mussa Khaitov, Nikolai Khaltaev, Jorg Kleine-Tebbe, Marek L. Kowalski, Vicky Kritikos, Inger Kull, Lisa Leonardini, Philip Lieberman, Brian Lipworth, Karin C. Lodrup Carlsen, Claudia C. Loureiro, Renaud Louis, Alpana Mair, Gert Marien, Bassam Mahboub, Joao Malva, Patrick Manning, Esteban De Manuel Keenoy, Gailen D. Marshall, Mohamed R. Masjedi, Jorge F. Maspero, Eve Mathieu-Dupas, Poalo M. Matricardi, Eric Melén, Elisabete Melo-Gomes, Eli O. Meltzer, Jacques Mercier, Neven Miculinic, Florin Mihaltan, Branislava Milenkovic, Giuliana Moda, Maria-Dolores Mogica-Martinez, Yousser Mohammad, Steve Montefort, Ricardo Monti, Mario Morais-Almeida, Ralf Mösges, Lars Münter, Antonella Muraro, Ruth Murray, Robert Naclerio, Luigi Napoli, Leila Namazova-Baranova, Hugo Neffen, Kristoff Nekam, Angelo Neou, Enrico Novellino, Dieudonné Nyembue, Robin O’Hehir, Ken Ohta, Kimi Okubo, Gabrielle Onorato, Solange Ouedraogo, Isabella Pali-Schöll, Susanna Palkonen, Peter Panzner, Hae-Sim Park, Jean-Louis Pépin, Ana-Maria Pereira, Oliver Pfaar, Ema Paulino, Jim Phillips, Davor Plavec, Ted A. Popov, Fabienne Portejoie, David Price, Emmanuel P. Prokopakis, Benoit Pugin, Filip Raciborski, Rojin Rajabian-Söderlund, Sietze Reitsma, Xavier Rodo, Antonino Romano, Nelson Rosario, Menahenm Rottem, Dermot Ryan, Johanna Salimäki, Mario M. Sanchez-Borges, Juan-Carlos Sisul, Dirceu Solé, David Somekh, Talant Sooronbaev, Milan Sova, Otto Spranger, Cristina Stellato, Rafael Stelmach, Charlotte Suppli Ulrik, Michel Thibaudon, Teresa To, Ana Todo-Bom, Peter V. Tomazic, Antonio A. Valero, Rudolph Valenta, Marylin Valentin-Rostan, Rianne van der Kleij, Olivier Vandenplas, Giorgio Vezzani, Frédéric Viart, Giovanni Viegi, Dana Wallace, Martin Wagenmann, De Y. Wang, Susan Waserman, Magnus Wickman, Dennis M. Williams, Gary Wong, Piotr Wroczynski, Panayiotis K. Yiallouros, Arzu Yorgancioglu, Osman M. Yusuf, Heahter J. Zar, Stéphane Zeng, Mario Zernotti, Luo Zhang, Nan S. Zhong, Mihaela Zidarn, the ARIA Study Group, and the MASK Study Group
Subjects: Health care transformation, Care pathways, Rhinitis, ARIA, MASK, POLLAR, Immunologic diseases. Allergy, RC581-607
Abstract: Abstract Background In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy. Main body As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted “patient activation”, (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care. Conclusion In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
Published: 2019
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9. Normal spirometry equates to normal impulse oscillometry in healthy subjects

Author: Brian Lipworth and Rory Chan
Subjects: Diseases of the respiratory system, RC705-779
Published: 2021
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10. An algorithm recommendation for the pharmacological management of allergic rhinitis in the UK: a consensus statement from an expert panel

Author: Brian Lipworth, Jon Newton, Bhaskar Ram, Iain Small, and Jürgen Schwarze
Subjects: Diseases of the respiratory system, RC705-779
Abstract: Abstract Allergic rhinitis is a frequent presenting problem in primary care in the UK, and has increased in prevalence over the last 30 years. When symptomatic, patients report significant reduction in their quality of life and impairment in school and work performance. Achieving adequate symptom control is pivotal to successful allergic rhinitis management, and relies mostly on pharmacotherapy. While it is recognised that most mild-moderate allergic rhinitis symptoms can be managed successfully in primary care, important gaps in general practitioner training in relation to allergic rhinitis have been identified. With the availability of new effective combination therapies, such as the novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (Dymista®; Meda), the majority of allergic rhinitis symptoms can be treated in the primary care setting. The primary objective of this consensus statement is to improve diagnosis and treatment of allergic rhinitis in primary care, and offer guidance on appropriate referral of difficult-to-treat patients into secondary care. The guidance provided herein outlines a sequential treatment pathway for allergic rhinitis in primary care that incorporates a considered approach to improve the management of allergic rhinitis symptoms and improve compliance and patient satisfaction with therapy. Adherence with this care pathway has the potential to limit the cost of providing effective allergic rhinitis management in the UK by avoiding unnecessary treatments and investigations, and avoiding the need for costly referrals to secondary care in the majority of allergic rhinitis cases. The fundamentals presented in this consensus article should apply in most health-care settings.
Published: 2017
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11. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure.

Author: Hans Bisgaard, Angela Simpson, Colin N A Palmer, Klaus Bønnelykke, Irwin McLean, Somnath Mukhopadhyay, Christian B Pipper, Liselotte B Halkjaer, Brian Lipworth, Jenny Hankinson, Ashley Woodcock, and Adnan Custovic
Subjects: Medicine
Abstract: BackgroundLoss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.Methods and findingsWe used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.ConclusionsWe have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
Published: 2008
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12. Phenotypic associations of medical polypectomy and revision surgery following endoscopic sinus surgery: a retrospective study of a single centre experience in Scotland

Author: Rasads Misirovs, Rory Chan, Kirsten Stewart, and Brian Lipworth
Subjects: Otorhinolaryngology, General Medicine
Published: 2023
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13. Severe asthma with fungal sensitization is associated with worse small airway dysfunction but similar symptom control

Author: Rory Chan and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published: 2023
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14. Clinical characteristics of the asthma bronchiectasis phenotype

Author: Rory Chan, Chary Duraikannu, and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published: 2023
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15. The Allergic Rhinitis and Its Impact on Asthma (ARIA) Approach of Value-Added Medicines: As-Needed Treatment in Allergic Rhinitis

Author: Jean Bousquet, Mondher Toumi, Bernardo Sousa-Pinto, Josep M. Anto, Anna Bedbrook, Wienczyslawa Czarlewski, Arunas Valiulis, Ignacio J. Ansotegui, Sinthia Bosnic-Anticevich, Luisa Brussino, G. Walter Canonica, Lorenzo Cecchi, Ivan Cherrez-Ojeda, Tomas Chivato, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Joao A. Fonseca, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Marek Jutel, Igor Kaidashev, Ludger Klimek, Violeta Kvedariene, Piotr Kuna, Désirée E. Larenas-Linnemann, Brian Lipworth, Mario Morais-Almeida, Joaquim Mullol, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham-Thi, Frederico S. Regateiro, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Luis Taborda-Barata, Maria Teresa Ventura, Arzu Yorgancioglu, Mihaela Zidarn, and Torsten Zuberbier
Subjects: Treatment, Value-added medicine, Allergic rhinitis, MASK-air, Repurposing, Humans, Disease Management, Immunology and Allergy, Rhinitis, Allergic, Mobile Applications, Asthma, Telemedicine
Abstract: Drug repurposing is a major field of value-added medicine. It involves investigating and evaluating existing drugs for new therapeutic purposes that address unmet healthcare needs. Several unmet needs in allergic rhinitis could be improved by drug repurposing. This could be game-changing for disease management. Current medications for allergic rhinitis are centered on continuous long-term treatment, and medication registration is based on randomized controlled trials carried out for a minimum of 14 days with adherence of 70% or greater. A new way of treating allergic rhinitis is to propose as-needed treatment depending on symptoms, rather than classical continuous treatment. This rostrum will discuss existing clinical trials on as-needed treatment for allergic rhinitis and real-world data obtained by the mobile health app MASK-air, which focuses on digitally-enabled, patient-centered care pathways.
Published: 2022
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16. The triple type 2 signature confers more frequent exacerbations and worse mid-expiratory flow in moderate to severe asthma

Author: Rory Chan and Brian Lipworth
Subjects: Immunology and Allergy
Published: 2023
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17. Clinical impact of obesity on oscillometry lung mechanics in adult asthmatics

Author: Rory Chan and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published: 2023
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18. Efficacy of biologic therapy on airway hyperresponsiveness in asthma

Author: Rory Chan and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Immunology, Immunology and Allergy
Published: 2023
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19. Have we reached our final destination with biologics in severe uncontrolled asthma?

Author: Brian Lipworth and Rory Chan
Subjects: Immunology and Allergy
Published: 2023
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20. Interactions between spirometry and oscillometry in patients with moderate to severe asthma

Author: Rory, Chan and Brian, Lipworth
Subjects: Pulmonary and Respiratory Medicine, Spirometry, Forced Expiratory Volume, Oscillometry, Humans, Asthma
Published: 2022
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21. Airflow obstruction in real life is associated with small airways dysfunction in moderate-to-severe asthma

Author: Rory Chan, Kirsten Stewart, and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Airway Obstruction, Pulmonary Disease, Chronic Obstructive, Immunology, Immunology and Allergy, Humans, Lung, Asthma
Published: 2022

22. Oscillometry bronchodilator response in adult moderate to severe eosinophilic asthma patients: A prospective cohort study

Author: Rory Chan and Brian Lipworth
Subjects: Adult, Spirometry, Oscillometry, Immunology, Immunology and Allergy, Humans, Prospective Studies, Pulmonary Eosinophilia, Asthma, Bronchodilator Agents
Published: 2022

23. Impaired Respiratory System Resistance and Reactance Are Associated With Bronchial Wall Thickening in Persistent Asthma

Author: Rory Chan, Chary Duraikannu, Mohamed Jaushal Thouseef, and Brian Lipworth
Subjects: Immunology and Allergy
Published: 2023
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24. Corticosteroid Protection Against COVID-19: Begin with the Nose

Author: Tara F. Carr, Brian Lipworth, and Rory Chan
Subjects: 2019-20 coronavirus outbreak, Editorial, medicine.anatomical_structure, Coronavirus disease 2019 (COVID-19), business.industry, medicine.drug_class, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine, Immunology and Allergy, Corticosteroid, business, Virology, Nose
Published: 2021
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25. A retrospective cohort study to evaluate the relationship of airway hyperresponsiveness to type 2 biomarkers in persistent asthma

Author: Rory Chan, Chris RuiWen Kuo, and Brian Lipworth
Subjects: Allergy, medicine.medical_specialty, business.industry, Airway hyperresponsiveness, Ocean Engineering, Retrospective cohort study, respiratory system, medicine.disease, respiratory tract diseases, Internal medicine, medicine, Safety, Risk, Reliability and Quality, business, Persistent asthma, Asthma
Abstract: irway hyperresponsiveness (AHR) is a hallmark of persistent asthma measured using direct or indirect airway bronchial challenge testing. The purpose of this study is to investigate the putative relationships between type 2 inflammatory biomarkers, airway geometry (FEV1 and FEF25-75) and specific IgE (RAST or skin prick) to AHR. We performed a retrospective analysis of our database (n = 131) of patients with asthma. Of these subjects, 75 had a histamine challenge and 56 had a mannitol challenge. Fractional exhaled nitric oxide (FeNO) and specific immunoglobulin E (IgE) but not blood eosinophils were significantly higher in patients with AHR to either histamine or mannitol. FEV1 % and FEF25 - 75 % were significantly lower in patients with AHR. Elevated Type 2 biomarkers including FeNO and specific IgE but not blood eosinophils were associated with AHR. Highlights: FeNO and specific IgE but not blood eosinophils are raised in patients with airway hyperresponsiveness.
Published: 2021
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26. Low-Grade B Cell Lymphoproliferative Disorder Masquerading as Chronic Rhinosinusitis

Author: Chris RuiWen Kuo, Rory Chan, and Brian Lipworth
Subjects: medicine.medical_specialty, business.industry, Chronic rhinosinusitis, chronic rhinosinusitis, Lymphoproliferative disorders, Primary care, lcsh:Otorhinolaryngology, medicine.disease, lcsh:RF1-547, Dermatology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030228 respiratory system, medicine, Bone marrow, Respiratory system, 030223 otorhinolaryngology, business, B-cell lymphoproliferative disorder, B cell
Abstract: Chronic rhinosinusitis (CRS) is one of the most common persistent disorders of the developed world, requiring input from various specialists including primary care physicians, otolaryngologists, respiratory physicians, and allergologists. B-cell lymphoproliferative disorders (BLPDs) are a heterogenous group of malignant conditions defined by an accumulation of mature B lymphocytes in the bone marrow, blood, and lymphoid tissues. We present a case report of an elderly man with rhinosinusitis-like symptoms and atypical features prompting further investigations that culminated in a diagnosis of BLPD.
Published: 2021
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27. Yin and yang of asthmatic inflammatory biomarkers and gene expression

Author: Brian Lipworth, Kirsten Stewart, and Rory Chan
Subjects: Eosinophils, Immunology, Gene Expression, Humans, Immunology and Allergy, Nitric Oxide, Asthma, Biomarkers
Published: 2022
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28. Clinical Associations of Mucus Plugging in Moderate to Severe Asthma

Author: Rory Chan, Chary Duraikannu, and Brian Lipworth
Subjects: Immunology and Allergy
Abstract: Mucus plugging is recognized as a contributory factor to airway obstruction and symptoms in persistent asthma.We aimed to determine phenotypic associations of mucus plugging in patients with moderate to severe asthma in a real-life clinic setting.Mucus plugs (MPs) were identified by a thoracic radiologist upon high-resolution computed tomography imaging. A MP score was subsequently calculated and analyzed along with type 2 biomarkers, spirometry, severe exacerbations, and asthma control for 126 patients with moderate to severe asthma before biologic therapy.Asthma patients with MP had significantly worse FEVPoorly controlled asthma patients with MPs exhibited significantly worse airflow obstruction and greater type 2 inflammation associated with more frequent severe exacerbations. Impaired spirometry, more frequent exacerbations, raised blood eosinophils, total IgE, and A fumigatus IgE increased the likelihood of MPs.
Published: 2022

29. Pragmatic reappraisal of long-acting muscarinic antagonists at steps 4 and 5 for persistent adult asthma

Author: Brian Lipworth, Kirsten E. Stewart, and Rory Chan
Subjects: Pulmonary and Respiratory Medicine, Adult, Adrenal Cortex Hormones, Immunology, Administration, Inhalation, Immunology and Allergy, Humans, Drug Therapy, Combination, Anti-Asthmatic Agents, Muscarinic Antagonists, Tiotropium Bromide, Asthma
Published: 2022

30. Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference

Author: Bernardo Sousa‐Pinto, Holger J. Schünemann, Ana Sá‐Sousa, Rafael José Vieira, Rita Amaral, Josep M. Anto, Ludger Klimek, Wienczyslawa Czarlewski, Joaquim Mullol, Oliver Pfaar, Anna Bedbrook, Luisa Brussino, Violeta Kvedariene, Desirée Larenas‐Linnemann, Yoshitaka Okamoto, Maria Teresa Ventura, Ioana Agache, Ignacio J. Ansotegui, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, Jan Brozek, G. Walter Canonica, Victoria Cardona, Pedro Carreiro‐Martins, Thomas Casale, Lorenzo Cecchi, Tomas Chivato, Derek K. Chu, Cemal Cingi, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Philippe Devillier, Patrik Eklund, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Zhanat Ispayeva, Marek Jutel, Piotr Kuna, Igor Kaidashev, Musa Khaitov, Helga Kraxner, Daniel Laune, Brian Lipworth, Renaud Louis, Michael Makris, Riccardo Monti, Mario Morais‐Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Milan Sova, Ana Todo‐Bom, Luis Taborda‐Barata, Sanna Toppila‐Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Olivier Vandenplas, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, Joao A. Fonseca, Jean Bousquet, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Comprehensive Health Research Centre (CHRC) - pólo NMS, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), and Publica
Subjects: allergic rhinitis, real-world data, allergen immunotherapy, co-medication, multivariable mixed-effects model, Immunology, Allergen immunotherapy, Rhinitis, Allergic, Adrenal Cortex Hormones, Desensitization, Immunologic, HDE ALER, Immunology and Allergy, Fluticasone, Humans, Rhinitis
Abstract: Funding Information: IA reports personal fees from Roxall, Menarini, UCB, Faes Farma, Sanofi, Bial, Amgen, Abbott, Bayer, Organon. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed‐Innov, personal fees from Purina, other from MASK‐air. VC reports personal fees from Thermofisher. PCM reports personal fees from Abbvie, AZ, Bial, GSK, Mylan, Medinfar, Novartis, Sanofi. LC reports personal fees from Malesci, Menarini, Astra Zeneca, Novartis. AC reports grants and personal fees from Astrazeneca, GSK, Sanofi, personal fees from Boehringer‐Ingelheim, Chiesi, Glenmark, Novartis, personal fees from Mylan, Abdi‐Ibrahim. PD reports personal fees and non‐financial support from Stallergenes Greer, ALK‐Abello, Astra Zeneca, CHIESI, MYLAN/Meda Pharma, Novartis, GlaxoSmithKline, Sanofi, IQVIA personal fees from MENARINI. JAFonseca reports participation in SME that has mHealth technologies for patients with asthma. JCI reports personal fees from Abbott Ecuador, Bago Bolivia, Faes Farma, Laboratorios Casasco, Sanofi. LK reports grants and personal fees from Allergopharma, LETI Pharma,MEDA/Mylan, Sanofi, personal fees from HAL Allergie, Allergy Therapeut., Cassella med, grants from ALK Abelló, Stallergenes, Quintiles, ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. VK reports other from Norameda, BerlinCHemie Menarini. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, Boehringer Ingelheim, Chiesi, GSK, Novartis, Polpharma. DLL reports personal fees from Allakos, Amstrong, Astrazeneca, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, Carnot, grants from Sanofi, Astrazeneca, Novartis, Circassia, UCB, GSK, Purina institute, Abvvie, Lilly, Pfizer. BL reports grants and personal fees from Meda, personal fees from Glenamrk. RL reports grants and personal fees from GSK, AZ, Chiesi, personal fees from Novartis, Sanofi. MM reports personal fees from Novartis, Gsk, Menarini, Az, Chiesi, Sanofi, Pfizer. RM reports personal fees from Angelini Pharma ALK, Allergopharma, Allergy Therapeutics, Friulchem, Hexal, Servier, Klosterfrau, Bayer, FAES, GSK, MSD, Johnson&Johnson, Meda, Stada, UCB, Nuvo, Menarini, Mundipharma, Pohl‐Boskamp, Laboratoire de la Mer, Sidroga, Lek, PRO‐AdWise, grants and personal fees from Bencard, Stallergenes, Ursapharm, HAL BV, grants from Leti, Optima, BitopAG, Hulka, Inmunotek, Cassella‐med GmbH & Co. KG, ASIT biotech, grants, personal fees and non‐financial support from Lofarma, non‐financial support from Roxall, Atmos, Bionorica, Otonomy, Ferrero, personal fees and non‐financial support from Novartis. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., GlaxoSmithKline, personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, Paul‐Martini‐Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, grants from Pohl‐Boskamp, Inmunotek S.L., Biomay, Circassia. NGPapadopoulos reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. ATB reports personal fees from AstraZeneca, GSK, Novartis, IQVIA/Abbvie, Mylan, Bial, Leti, grants and personal fees from Teva. STS reports personal fees from ERT, Roche products, Novartis, Sanofi Pharma, AstraZeneca, ALK‐ Abelló grants from Glaxo Smith Kline. IT reports grants from GSK, Boehringer Ingelheim, AZ, personal fees from Novartis, Astra Zeneca, Chiesi, TZ reports Organizational affiliations: Committee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF). President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). Funding Information: MASK‐air® has been supported by EU grants (POLLAR, EIT Health; Structural and Development Funds, Twinning, EIP on AHA and H2020) and educational grants from Mylan‐Viatris, ALK, GSK, Novartis and Uriach 1 1 Publisher Copyright: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80). Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines. publishersversion published
Published: 2022
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31. Forced Vital Capacity and Low Frequency Reactance Area Measurements Are Associated with Asthma Control and Exacerbations

Author: Rory Chan and Brian Lipworth
Subjects: Pulmonary and Respiratory Medicine, Adrenal Cortex Hormones, Spirometry, Forced Expiratory Volume, Vital Capacity, Humans, Lung, Asthma
Abstract: Introduction Forced vital capacity (FVC) is often preserved in severe asthma unless there is evidence of either airway remodelling or air trapping. Area under the reactance curve (AX) can be used to assess small airways dysfunction related lung stiffness and is related to disease control in severe asthma. Methods We explore if there may be a potential synergistic interaction between FVC and AX in terms of impaired asthma control as ACQ and exacerbations requiring oral corticosteroids (OCS). We pragmatically defined Results Patients with combined impairment of FVC and AX had significantly worse asthma control as higher ACQ, more severe exacerbations requiring OCS and worse spirometry (FEV1 and FEF25–75) than those with impaired FVC but preserved AX. Conclusion This in turn supports using both spirometry and oscillometry to characterise airway physiology more comprehensively in patients with more severe asthma.
Published: 2022

32. Allopurinol in Patients with Pulmonary Hypertension Associated with Chronic Lung Disease

Author: Patrick Sk Liu-Shiu-Cheong, Jonathan R. Weir-McCall, Allan D. Struthers, Brian Lipworth, and J. Graeme Houston
Subjects: Spirometry, medicine.medical_specialty, medicine.drug_class, Allopurinol, Placebo, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ventricular hypertrophy, Internal medicine, medicine, 030212 general & internal medicine, Xanthine oxidase, Xanthine oxidase inhibitor, COPD, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Pulmonary hypertension, respiratory tract diseases, 030228 respiratory system, chemistry, Cardiology, business, medicine.drug
Abstract: Background Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD). Methods We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT). Results Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FEV1 60% and resting SpO2 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI -4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation. Conclusion Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation.
Published: 2020
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33. Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics

Author: Chris RuiWen Kuo, Sunny Jabbal, and Brian Lipworth
Subjects: Adult, Male, Spirometry, medicine.medical_specialty, Time Factors, Immunology, Muscarinic Antagonists, Gastroenterology, chemistry.chemical_compound, Adrenal Cortex Hormones, Internal medicine, Administration, Inhalation, medicine, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Tiotropium Bromide, Pack-year, Adrenergic beta-2 Receptor Agonists, Lung, Asthma, Cross-Over Studies, Smokers, biology, medicine.diagnostic_test, business.industry, Nebulizers and Vaporizers, Inhaler, Smoking, Olodaterol, Recovery of Function, respiratory system, Lama, biology.organism_classification, medicine.disease, Crossover study, Benzoxazines, respiratory tract diseases, Drug Combinations, Treatment Outcome, Scotland, chemistry, Female, Airway, business
Abstract: Background Smoking worsens underlying asthma inflammation and also induces resistance to inhaled corticosteroids (ICS). Small airways dysfunction measured by impulse oscillometry (IOS) is associated with worse control. Objectives We investigated the effects on small airways of adding long-acting beta-agonist (LABA) alone or with long-acting muscarinic antagonist (LAMA) to ICS in asthmatic smokers. Methods Sixteen current smokers were enrolled: mean age 44 year, FEV1 84%, FEF25-75 47%, R5 158%, ACQ 1.69, 20 pack year . Patients were converted to a reference ICS as HFA-BDP during initial run-in at median dose of 800 µg/day. Open label olodaterol 5 µg od (OLO) or olodaterol 5 µg/tiotropium 5 µg od (OLO/TIO) was added to HFA-BDP for median duration of 3 weeks in a randomized cross over design, including run-in and washout periods on HFA-BDP. IOS and spirometry were measured after each treatment (BDP/OLO/TIO or BDP/OLO) and at baseline after run-in and washout (BDP). Results After chronic dosing, IOS outcomes at trough except for R20 were all significantly improved with OLO/TIO compared to OLO. For the primary end-point of total airway resistance (as R5), the mean difference (95%CI) at trough was 0.06 (0.015-0.10) kPa/l/s, peripheral airways resistance (as R5-R20) 0.03 (0.003-0.06) kPa/l/s, peripheral lung reactance area (as AX) 0.38 (0.08-0.68) kPa/l and resonant frequency (as RF) 2.28 (0.45-4.12) Hz. FEF25-75 at trough was also better with OLO/TIO vs TIO: 0.93 (0.86 - 0.95) l/s while FEV1 was not different. Conclusions ICS/LABA/LAMA was superior to ICS/LABA on trough small airway outcomes in asthma patients who smoke.
Published: 2020
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34. Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Lung Function versus Monotherapies in GOLD Category A Patients with COPD: Pooled Data from the Phase III PINNACLE Studies

Author: Colin Reisner, Klaus F. Rabe, Martin Jenkins, Brian Lipworth, Ubaldo J. Martin, Fernando J. Martinez, and Samir Arora
Subjects: Male, Time Factors, Exacerbation, bronchodilator, muscarinic antagonist, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Forced Expiratory Volume, Formoterol Fumarate, Bronchodilator, β2- agonist, Multicenter Studies as Topic, 030212 general & internal medicine, Lung, Original Research, Randomized Controlled Trials as Topic, education.field_of_study, COPD, integumentary system, co-suspension delivery technology, General Medicine, Middle Aged, Metered-dose inhaler, Obstructive lung disease, Bronchodilator Agents, Drug Combinations, Treatment Outcome, Female, medicine.medical_specialty, medicine.drug_class, Population, Muscarinic Antagonists, International Journal of Chronic Obstructive Pulmonary Disease, Placebo, 03 medical and health sciences, Internal medicine, Administration, Inhalation, medicine, Humans, Metered Dose Inhalers, education, Adrenergic beta-2 Receptor Agonists, Aged, business.industry, lung function, Recovery of Function, medicine.disease, Glycopyrrolate, Clinical Trials, Phase III as Topic, 030228 respiratory system, business
Abstract: Fernando J Martinez,1 Klaus F Rabe,2 Brian J Lipworth,3 Samir Arora,4 Martin Jenkins,5 Ubaldo J Martin,6 Colin Reisner6,7 1Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, NY, USA; 2Department of Pneumonology, LungenClinic Grosshansdorf and Christian-Albrechts University Kiel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 3Division of Molecular and Clinical Medicine, Scottish Centre for Respiratory Research, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK; 4Aventiv Research Inc., Columbus, OH, USA; 5Global Medicines Development, AstraZeneca, Cambridge, UK; 6Research and Development, AstraZeneca, Gaithersburg, MD, USA; 7R&D Biopharmaceuticals, AstraZeneca, Morristown, NJ, USACorrespondence: Fernando J MartinezJoan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, 525 E 68th Street, Room M-522, Box 130, New York, NY 10065, USATel +1646 962 2748Email fjm2003@med.cornell.eduBackground: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends a short-acting bronchodilator or single long-acting bronchodilator as an initial pharmacological treatment for GOLD category A patients with COPD. We pooled data from the PINNACLE-1, -2, and -4 studies to evaluate the efficacy and safety of the dual bronchodilator fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), formulated using co-suspension delivery technology, in GOLD category A patients with moderate-to-very severe COPD.Materials and Methods: PINNACLE-1, -2, and -4 were Phase III, randomized, double-blind, parallel-group, multicenter studies (NCT01854645, NCT01854658, and NCT02343458). Patients received 24 weeks’ treatment with GFF MDI 18/9.6 μg, glycopyrrolate (GP) MDI 18 μg, formoterol fumarate (FF) MDI 9.6 μg, or placebo MDI twice daily. GOLD category A patients were identified based on a COPD Assessment Test score of 1), peak change from baseline in FEV1 within 2 hrs post-dose, and adverse events (AEs).Results: The pooled intent-to-treat population comprised 729 GOLD category A patients. GFF MDI significantly improved morning pre-dose trough FEV1 at Week 24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences 54 mL, 62 mL, and 188 mL, respectively; all p≤0.0053), and peak FEV1 at Week 24 versus GP MDI, FF MDI, and placebo MDI (LSM differences 124 mL, 104 mL, and 307 mL, respectively; all p
Published: 2020
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35. Behavioural patterns in allergic rhinitis medication in Europe: A study using MASK-air

Author: Bernardo, Sousa-Pinto, Ana, Sá-Sousa, Rafael José, Vieira, Rita, Amaral, Ludger, Klimek, Wienczyslawa, Czarlewski, Josep M, Antó, Oliver, Pfaar, Anna, Bedbrook, Violeta, Kvedariene, Maria Teresa, Ventura, Ignacio J, Ansotegui, Karl-Christian, Bergmann, Luisa, Brussino, G Walter, Canonica, Victoria, Cardona, Pedro, Carreiro-Martins, Tomas, Casale, Lorenzo, Cecchi, Tomás, Chivato, Derek K, Chu, Cemal, Cingi, Elísio M, Costa, Alvaro A, Cruz, Giulia, De Feo, Philippe, Devillier, Wytske J, Fokkens, Mina, Gaga, Bilun, Gemicioğlu, Tari, Haahtela, Juan Carlos, Ivancevich, Zhanat, Ispayeva, Marek, Jutel, Piotr, Kuna, Igor, Kaidashev, Helga, Kraxner, Désirée E, Larenas-Linnemann, Daniel, Laune, Brian, Lipworth, Renaud, Louis, Michael, Makris, Riccardo, Monti, Mario, Morais-Almeida, Ralph, Mösges, Joaquim, Mullol, Mikaëla, Odemyr, Yoshitaka, Okamoto, Nikolaos G, Papadopoulos, Vincenzo, Patella, Nhân, Pham-Thi, Frederico S, Regateiro, Sietze, Reitsma, Philip W, Rouadi, Boleslaw, Samolinski, Milan, Sova, Ana, Todo-Bom, Luis, Taborda-Barata, Peter Valentin, Tomazic, Sanna, Toppila-Salmi, Joaquin, Sastre, Ioanna, Tsiligianni, Arunas, Valiulis, Olivier, Vandenplas, Dana, Wallace, Susan, Waserman, Arzu, Yorgancioglu, Mihaela, Zidarn, Torsten, Zuberbier, João A, Fonseca, and Jean, Bousquet
Subjects: Europe, Habits, Histamine Antagonists, Humans, Rhinitis, Allergic, Rhinitis
Abstract: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data.We analysed 2015-2020 MASK-airWe analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral HAllergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.
Published: 2022

36. Mepolizumab response in severe chronic rhinosinusitis with nasal polyps is dissociated from blood eosinophil levels

Author: Brian Lipworth, Rory Chan, Rasads Misirovs, and Kirsten Stewart
Subjects: Eosinophils, Nasal Polyps, Immunology, Chronic Disease, Immunology and Allergy, Humans, Sinusitis, Antibodies, Monoclonal, Humanized, Rhinitis
Published: 2022

37. Consistent trajectories of rhinitis control and treatment in 16,177 weeks: The MASK-air® longitudinal study

Author: Bernardo Sousa‐Pinto, Holger J. Schünemann, Ana Sá‐Sousa, Rafael José Vieira, Rita Amaral, Josep M. Anto, Ludger Klimek, Wienczyslawa Czarlewski, Joaquim Mullol, Oliver Pfaar, Anna Bedbrook, Luisa Brussino, Violeta Kvedariene, Désirée E. Larenas‐Linnemann, Yoshitaka Okamoto, Maria Teresa Ventura, Ioana Agache, Ignacio J. Ansotegui, Karl C. Bergmann, Sinthia Bosnic‐Anticevich, G. Walter Canonica, Victoria Cardona, Pedro Carreiro‐Martins, Thomas Casale, Lorenzo Cecchi, Tomas Chivato, Derek K. Chu, Cemal Cingi, Elísio M. Costa, Alvaro A. Cruz, Stefano Del Giacco, Philippe Devillier, Patrik Eklund, Wytske J. Fokkens, Bilun Gemicioglu, Tari Haahtela, Juan Carlos Ivancevich, Zhanat Ispayeva, Marek Jutel, Piotr Kuna, Igor Kaidashev, Musa Khaitov, Helga Kraxner, Daniel Laune, Brian Lipworth, Renaud Louis, Michael Makris, Riccardo Monti, Mario Morais‐Almeida, Ralph Mösges, Marek Niedoszytko, Nikolaos G. Papadopoulos, Vincenzo Patella, Nhân Pham‐Thi, Frederico S. Regateiro, Sietze Reitsma, Philip W. Rouadi, Boleslaw Samolinski, Aziz Sheikh, Milan Sova, Ana Todo‐Bom, Luis Taborda‐Barata, Sanna Toppila‐Salmi, Joaquin Sastre, Ioanna Tsiligianni, Arunas Valiulis, Olivier Vandenplas, Dana Wallace, Susan Waserman, Arzu Yorgancioglu, Mihaela Zidarn, Torsten Zuberbier, Joao A. Fonseca, Jean Bousquet, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Ear, Nose and Throat, AII - Inflammatory diseases, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, Helsinki University Hospital Area, and Department of Pathology
Subjects: Patient-reported outcomes, real-world data, Respiratory Medicine and Allergy, Immunology, Oto-rino-laryngologi, Rhinitis* / epidemiology, Real-world data, rhinitis, Otorhinolaryngology, patient-reported outcomes, Surveys and Questionnaires, HDE ALER, 3121 General medicine, internal medicine and other clinical medicine, Humans, Immunology and Allergy, Longitudinal Studies, Mobile health, mobile health, Telemedicine, Lungmedicin och allergi, Rhinitis
Abstract: Data de publicació electrònica: 03-11-2022 Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.
Published: 2022
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38. Importance of β2-receptor function in premenstrual asthma

Author: Kirsten E. Stewart, Rory Chan, and Brian Lipworth
Subjects: Immunology and Allergy
Published: 2022
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39. Anti-inflammatory reliever therapy for asthma

Author: Brian Lipworth, Chris RuiWen Kuo, and Rory Chan
Subjects: Male, Pulmonary and Respiratory Medicine, Budesonide, medicine.medical_specialty, medicine.drug_class, Immunology, Anti-Inflammatory Agents, MEDLINE, Anti-inflammatory, Internal medicine, Administration, Inhalation, medicine, Budesonide, Formoterol Fumarate Drug Combination, Humans, Immunology and Allergy, Albuterol, Anti-Asthmatic Agents, Asthma, Inhalation, business.industry, Nebulizers and Vaporizers, medicine.disease, Bronchodilator Agents, Female, business, medicine.drug
Published: 2020
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40. Benefit:Risk Profile of Budesonide in Obstructive Airways Disease

Author: Ralph Brattsand, Brian Lipworth, and Donald P. Tashkin
Subjects: Budesonide, Chronic Obstructive, medicine.medical_specialty, Combination therapy, Anti-Inflammatory Agents, Review Article, Pulmonary Disease, Maintenance therapy, Humans, Medicine, Pharmacology (medical), Pharmacology & Pharmacy, Intensive care medicine, Adverse effect, Asthma, COPD, business.industry, Pharmacology and Pharmaceutical Sciences, medicine.disease, respiratory tract diseases, Formoterol, business, Airway, medicine.drug
Abstract: Airway inflammation is a major contributing factor in both asthma and chronic obstructive pulmonary disease (COPD) and represents an important target for treatment. Inhaled corticosteroids (ICS) as monotherapy or in combination therapy with long-acting β2-agonists or long-acting muscarinic antagonists are used extensively in the treatment of asthma and COPD. The development of ICS for their anti-inflammatory properties progressed through efforts to increase topical potency and minimise systemic potency and through advances in inhaled delivery technology. Budesonide is a potent, non-halogenated ICS that was developed in the early 1970s and is now one of the most widely used lung medicines worldwide. Inhaled budesonide's physiochemical and pharmacokinetic/pharmacodynamic properties allow it to reach a rapid and high airway efficacy due to its more balanced relationship between water solubility and lipophilicity. When absorbed from the airways and lung tissue, its moderate lipophilicity shortens systemic exposure, and its unique property of intracellular esterification acts like a sustained release mechanism within airway tissues, contributing to its airway selectivity and a low risk of adverse events. There is a large volume of clinical evidence supporting the efficacy and safety of budesonide, both alone and in combination with the fast- and long-acting β2-agonist formoterol, as maintenance therapy in patients with asthma and with COPD. The combination of budesonide/formoterol can also be used as an as-needed reliever with anti-inflammatory properties, with or without regular maintenance for asthma, a novel approach that is already approved by some country-specific regulatory authorities and currently recommended in the Global Initiative for Asthma (GINA) guidelines. Budesonide remains one of the most well-established and versatile of the inhaled anti-inflammatory drugs. This narrative review provides a clinical reappraisal of the benefit:risk profile of budesonide in the management of asthma and COPD.
Published: 2019
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41. Considerations of a real life pragmatic clinical trial in adolescent asthma

Author: Brian Lipworth, Tom Ruffles, and Somnath Mukhopadhyay
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, business.industry, MEDLINE, Primary care, medicine.disease, Pragmatic trial, Asthma, Clinical trial, medicine, Humans, Intensive care medicine, business, Bit (key)
Abstract: A pragmatic trial design was used to elucidate potential effects of genotype directed asthma prescribing in a real life primary care settinghttps://bit.ly/2PpYavS
Published: 2021

42. Real-life small airway outcomes in severe asthma patients receiving biologic therapies

Author: Chris RuiWen Kuo, Brian Lipworth, and Rory Chan
Subjects: medicine.medical_specialty, business.industry, Severe asthma, Respiratory System, Biologic therapies, MEDLINE, Asthma, Biological Therapy, Text mining, Humans, Immunology and Allergy, Medicine, Anti-Asthmatic Agents, Airway, business, Intensive care medicine
Published: 2021
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43. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author: Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.
Subjects: MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
Published: 2020
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44. Combined medical and surgical therapy for chronic rhinosinusitis with nasal polyposis

Author: Brian Lipworth, Rory Chan, Rasads Misirovs, and Kirsten Stewart
Subjects: Pulmonary and Respiratory Medicine
Published: 2022
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45. Inhaled triple therapy and airway hyperresponsiveness in persistent asthma

Author: Rory Chan, Brian Lipworth, Chris RuiWen Kuo, and Sunny Jabbal
Subjects: Pulmonary and Respiratory Medicine, business.industry, Immunology, Airway hyperresponsiveness, MEDLINE, Muscarinic Antagonists, Adrenergic beta-Agonists, medicine.disease, Asthma, Adrenal Cortex Hormones, Forced Expiratory Volume, medicine, Immunology and Allergy, Humans, Mannitol, Persistent asthma, business
Published: 2020

46. Emerging pharmacotherapy for COVID-19

Author: Brian Lipworth, Chris RuiWen Kuo, and Rory Chan
Subjects: Combination therapy, medicine.drug_class, Upstream and downstream (transduction), medicine.medical_treatment, Pneumonia, Viral, Anti-Inflammatory Agents, Disease, Bioinformatics, Antiviral Agents, Education, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Immune system, Pharmacotherapy, Medicine, Humans, 030212 general & internal medicine, Enzyme Inhibitors, Pandemics, Alanine, business.industry, SARS-CoV-2, COVID-19, Hydroxychloroquine, General Medicine, Adenosine Monophosphate, Cytokine, Cytokines, Antiviral drug, business, Coronavirus Infections, medicine.drug
Abstract: Broadly speaking, pharmacological treatments for COVID-19 can be divided into those acting on upstream pathways early on in the disease process via suppression of viral replication or by inhibiting cell entry, and those acting on downstream pathways later on via selective attenuation of the adaptive immune cytokine-mediated inflammatory response. The antiviral drug remdesivir has been shown to shorten duration of disease while interferon beta-1b may speed up viral clearance. The results with hydroxychloroquine have thus far been rather disappointing. Trials with selective cytokine blockers including anti-interleukin-1 (anti-IL-1) and anti-interleukin-6 (anti-IL-6), have shown some promise in more severe cases, with further confirmation being required from large-scale phase-3 randomised controlled trials. The likelihood is that combination therapy addressing both upstream and downstream pathways may be required to prevent progression of severe COVID-19 infection in susceptible older patients with comorbidities and we believe further studies are now warranted to specifically target such at-risk groups who are more prone to worse outcomes.
Published: 2020

47. Use of inhaled corticosteroids in asthma and coronavirus disease 2019: Keep calm and carry on

Author: Brian, Lipworth, Rory, Chan, and Chris RuiWen, Kuo
Subjects: Pneumonia, Viral, Peptidyl-Dipeptidase A, Viral Nonstructural Proteins, Severity of Illness Index, Dexamethasone, Article, Betacoronavirus, Adrenal Cortex Hormones, Administration, Inhalation, Endoribonucleases, Humans, Anti-Asthmatic Agents, Pandemics, Interleukin-6, SARS-CoV-2, Tumor Necrosis Factor-alpha, Interleukin-8, Serine Endopeptidases, COVID-19, Asthma, Gene Expression Regulation, Host-Pathogen Interactions, Receptors, Virus, Angiotensin-Converting Enzyme 2, Coronavirus Infections, Cytokine Release Syndrome
Published: 2020

48. Defining a severe asthma super-responder: findings from a Delphi process

Author: Delphi panel: Adel Mansur, Aikaterini, Detoraki, Alan, Altraja, Alan, James, Alexandra, Nanzer-Kelly, Andréanne, Côté, Andrew, Menzies-Gow, Andriana, Papaioannou, Anne-Maree, Cheffins, Arnaud, Bourdin, Bassam, Mahboub, Brian, Lipworth, Carlos Andrés Celis-Preciado, Carlos, Torres-Duque, Caterina, Bucca, Celeste, Porsbjerg, Charlotte, Ulrik, Chris, Corrigan, Christian, Taube, Claude, Farah, Constance, Katelaris, David, Langton, Dermot, Ryan, Désirée, Larenas-Linnemann, Eleftherios, Zervas, Enrico, Heffler, Flavia, Hoyte, Francesca, Puggioni, George, Christoff, Giorgio Walter Canonica, Giovanna Elisiana Carpagnano, Giuseppe, Guida, Gregory, Katsoulotos, Guy, Brusselle, Hitashi, Rupani, Hubertus, Jersmann, Ian, Clifton, Jaideep, Dhariwal, James, Fingleton, Jane, Duke, Janet, Rimmer, Douglass, Jo, João, Fonseca, Job van Boven, John, Corless, John, Harrington, Jorge, Maspero, José Luis Miguel, Kanok, Pipatvech, Karrinda, Kenny, Kenneth, Chapman, Konstantinos, Kostikas, Lauri, Lehtimäki, Li Ping Chung, Liam, Heaney, Liang-Wen, Hang, Louis-Philippe, Boulet, Luis, Perez-de-Llano, Ricciardi, Luisa, Majdy, Idrees, Manlio, Milanese, Maria Elisabetta Conte, Maria Teresa Costantino, Mariko Koh Siyue, Mark, Fitzgerald, Mark, Hew, Matthew, Peters, Ming-Ju, Tsai, Mitesh, Patel, Mohammad Hashim Khan, Mohsen, Sadatsafavi, Mona, Al-Ahmad, Mona-Rita, Yacoub, Mónica De Gennaro, Naghmeh, Radhakrishna, Nicola Alexander Hanania, Nikolaos, Papadopoulos, Njira, Lugogo, Norma, Linaker, Nunzio, Crimi, Paddy, Dennison, Parameswaran, Nair, Patrick David Mitchell, Paul, O’Byrne, Paul, Pfeffer, Paula, Kauppi, Pauline, Hughes, Peter, Middleton, Peter, Wark, Philip, Bardin, Pin-Kuei, Fu, Praveen, Akuthota, Rekha, Chaudhuri, Ricardo, Campos, Riyard, Al-Lehebi, Roberta, Parente, Rovira, Francisco, Sally, Wenzel, Santus, Pierachille, Shrikant, Pawar, Stelios, Loukides, Stephen, Fowler, Tara, Mackenzie, Thomas, Brown, Tze Lee Tan, Unnur, Björnsdóttir, Vanessa, Mcdonald, Veronica, Lawriwskyj, Vibeke, Backer, Violina, Vasileva, Ying-Chun, Chien, and Zinta, Harrington.
Published: 2020

49. Improved lung function and patient-reported outcomes with co-suspension delivery technology glycopyrrolate/formoterol fumarate metered dose inhaler in COPD: a randomized Phase III study conducted in Asia, Europe, and the USA

Author: Rongchang Chen, Yasuhiro Gon, Ubaldo J. Martin, David Collier, Nanshan Zhong, Brian Lipworth, Colin Reisner, Koichi Nishi, Samir Arora, Andrea Maes, and Shahid Siddiqui
Subjects: Male, Internationality, bronchodilator, muscarinic antagonist, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Bronchodilator, Forced Expiratory Volume, Formoterol Fumarate, Clinical endpoint, Medicine, 030212 general & internal medicine, Original Research, Aged, 80 and over, education.field_of_study, COPD, integumentary system, co-suspension delivery technology, General Medicine, Middle Aged, Metered-dose inhaler, Bronchodilator Agents, Respiratory Function Tests, Europe, Treatment Outcome, Drug Therapy, Combination, Female, β2-agonist, Adult, medicine.medical_specialty, Asia, medicine.drug_class, Population, International Journal of Chronic Obstructive Pulmonary Disease, Placebo, Drug Administration Schedule, 03 medical and health sciences, Double-Blind Method, Internal medicine, Administration, Inhalation, Humans, Metered Dose Inhalers, Patient Reported Outcome Measures, education, Adverse effect, Aged, Dose-Response Relationship, Drug, business.industry, medicine.disease, Glycopyrrolate, United States, 030228 respiratory system, business, Follow-Up Studies
Abstract: Brian J Lipworth,1 David J Collier,2 Yasuhiro Gon,3 Nanshan Zhong,4 Koichi Nishi,5 Rongchang Chen,4 Samir Arora,6 Andrea Maes,7 Shahid Siddiqui,8 Colin Reisner,7,8 Ubaldo J Martin8 1Scottish Centre for Respiratory Research, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK; 2William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 3Itabashi Hospital, Nihon University School of Medicine, Itabashi, Tokyo, Japan; 4Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan; 6Aventiv Research Inc., Columbus, OH, USA; 7Pearl – a member of the AstraZeneca group, Morristown, NJ, USA; 8AstraZeneca, Gaithersburg, MD, USA Background: COPD is a major global cause of mortality and morbidity. PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD. Methods: In this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6µg, glycopyrrolate (GP) MDI 18µg, formoterol fumarate (FF) MDI 9.6µg, or placebo MDI (all twice daily) for 24weeks. Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed. Results: Of the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2years, 74.1% male, and 40.2% Asian). GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72mL, respectively; all P
Published: 2018

50. Current appraisal of single inhaler triple therapy in COPD

Author: Brian Lipworth, Sunny Jabbal, and Chris RuiWen Kuo
Subjects: Male, Budesonide, Exacerbation, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, exacerbation, 0302 clinical medicine, Adrenal Cortex Hormones, 030212 general & internal medicine, Randomized Controlled Trials as Topic, COPD, biology, General Medicine, Middle Aged, Lama, Bronchodilator Agents, Treatment Outcome, Editorial, Drug Therapy, Combination, Female, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, medicine.medical_specialty, Muscarinic Antagonists, International Journal of Chronic Obstructive Pulmonary Disease, Risk Assessment, inhaled corticosteroid, Fluticasone propionate, 03 medical and health sciences, Internal medicine, Administration, Inhalation, medicine, Humans, long-acting muscarinic antagonist, Adrenergic beta-2 Receptor Agonists, Aged, business.industry, Nebulizers and Vaporizers, Inhaler, lung function, Beclometasone dipropionate, medicine.disease, biology.organism_classification, long-acting beta-agonist, Pneumonia, 030228 respiratory system, business, Follow-Up Studies
Abstract: Brian Lipworth, Chris RuiWen Kuo, Sunny Jabbal Division of Molecular & Clinical Medicine, Scottish Centre for Respiratory Research, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK Abstract: A single inhaler containing inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA) is a more convenient way of delivering triple therapy in patients with COPD. Single triple therapy has been shown to be superior at reducing exacerbations and improving quality of life compared to LABA/LAMA, especially in patients with a prior history of frequent exacerbations and blood eosinophilia, who have ICS responsive disease. The corollary is that patients with infrequent exacerbations who are noneosinophilic may be safely de-escalated from triple therapy to LABA/LAMA without loss of control. Pointedly, there is a substantially increased risk of pneumonia associated with the triple therapy containing fluticasone furoate but not beclometasone dipropionate or budesonide. Since triple therapy is also better than ICS/LABA at reducing exacerbations and improving lung function, symptoms, and quality of life, this brings into question the rationale for using ICS/LABA. Hence, we propose a simplified pragmatic decision process based on symptoms, prior to exacerbation history, and blood eosinophils to select which patients should be given a single triple inhaler or LABA/LAMA. Differences in patient preference of inhaler device, formulations and drugs will also determine which triple inhaler prescribers elect to use. Keywords: COPD, inhaled corticosteroid, long-acting beta-agonist, long-acting muscarinic antagonist, lung function, exacerbation
Published: 2018
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