Application of structured statistical analyses to identify a biomarker predictive of enhanced tralokinumab efficacy in phase III clinical trials for severe, uncontrolled asthma

• Technical advance
• OPEN Open Peer Review
• 
  

BMC Pulmonary Medicine

Mattis Gottlow, 

David J. Svensson, 

Ilya Lipkovich, 

Monika Huhn, 

Karin Bowen, 

Peter Wessman & 

Gene Colice 

BMC Pulmonary Medicinevolume 19, Article number: 129 (2019) | Download Citation

Abstract

Background

Staggered trial design of STRATOS 1 and 2. Q2W,
every 2 weeks; Q4W, every 4 weeks; SC, subcutaneous

Tralokinumab is an anti–interleukin (IL)-13 monoclonal antibody investigated for the treatment of severe, uncontrolled asthma in two Phase III clinical trials, STRATOS 1 and 2. The STRATOS 1 biomarker analysis plan was developed to identify biomarker(s) indicative of IL-13 activation likely to predict tralokinumab efficacy and define a population in which there was an enhanced treatment effect; this defined population was then tested in STRATOS 2.

Increased platelet activating factor levels in chronic spontaneous urticaria predicts refractoriness to antihistamine treatment: an observational study

• Research
• OPEN
• Clinical and Translational Allergy

• Bastsetseg Ulambayar, 
• Eun-Mi Yang, 
• Hyun-Young Cha, 
• Yoo-Seob Shin, 
• Hae-Sim Park & 
• Young-Min Ye 

Clinical and Translational Allergyvolume 9, Article number: 33 (2019) | Download Citation

Abstract

Background

Platelet activating factor (PAF) is an endogenous, active phospholipid released from inflammatory cells, platelets, and endothelial cells, and is involved in the regulation of immune responses. Degradation of PAF by PAF acetylhydrolase (PAF-AH) has been shown to be associated with anaphylaxis, asthma, and peanut allergy.

Serum levels of PAF (a) and PAF-AH (b) and PAF-AH to PAF ratio (c)
in patients with CSU and NCs. PAF platelet activating factor, PAF-AH platelet activating factor acetylhydrolase, CSU chronic spontaneous urticaria, NC healthy normal control. p values
were calculated by Mann–Whitney U-test

The purpose of this study was to investigate relationships among clinical parameters, including urticaria severity and treatment responsiveness, and PAF and PAF-AH levels in sera from patients with chronic spontaneous urticaria (CSU).

Elderly versus younger patients with hereditary angioedema type I/II: patient characteristics and safety analysis from the Icatibant Outcome Survey

Clinical and Translational Allergy
•   Research
• OPEN

• Anette Bygum, 
• Teresa Caballero, 
• Anete S. Grumach, 
• Hilary J. Longhurst, 
• Laurence Bouillet, 
• Werner Aberer, 
• Andrea Zanichelli, 
• Jaco Botha, 
• Irmgard Andresen, 
• Marcus Maurer & 
• for the IOS Study Group

Clinical and Translational Allergyvolume 9, Article number: 37 (2019) | Download Citation

Abstract

Background

Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by recurrent swelling in subcutaneous or submucosal tissues. Symptoms often begin by age 5–11 years and worsen during puberty, but attacks can occur at any age and recur throughout life. Disease course in elderly patients is rarely reported.

Comparison of two multiplex arrays in the diagnostics of allergy

Clinical and Translational Allergy 
• Research
• Open Access
• 
  

• Jana Bojcukova

,

Tomas Vlas,

Peter Forstenlechner and

Petr Panzner

Clinical and Translational Allergy20199:31

Abstract

Kappa analysis between ISAC and ALEX

The objective of this analysis was to compare the multiplex ImmunoCAP ISAC (Thermo Fisher Scientific, Sweden) and the multiplex Alex Allergy Explorer (Macro Array Diagnostics GmbH, Austria) platform on specific IgE to grass pollen (Phl p 1, Phl p 5), tree pollen (Bet v 1), house dust mites (Der p 1, Der p 2) and cat (Fel d 1) allergens in allergic patients.

Molecular clustering of genes related to the atopic syndrome: Towards a more tailored approach and personalized medicine?

• Research
• Open Access

• Jill de Wit†View ORCID ID profile,
• Rogier T. A. van Wijck†,
• Virgil A. S. H. Dalm,
• Kristen L. Snyder,
• Joan E. E. Totté,
• Suzanne G. M. A. Pasmans†,
• Peter J. van der Spek†Email author and
• the Academic Center of Excellence (ACE) workgroups Allergic Diseases and Rare Immunological Disease Centre (RIDC)

†Contributed equally

Clinical and Translational Allergy20199:34

Abstract

Background

Venn diagram illustrating the overlap of the disease causing genes
of monogenic primary immunodeficiency diseases and the atopy-related genes
identified in the Human Gene Mutation Database

The atopic syndrome consists of heterogeneous manifestations, in which multiple associated genetic loci have recently been identified. It is hypothesized that immune dysregulation plays a role in the pathogenesis. In primary immunodeficiency diseases (PIDs), which are often monogenic immunodysregulation disorders, the atopic syndrome is a frequently occurring comorbidity.

2019 ARIA Care pathways for allergen immunotherapy

REVIEW 

 

Free Access

Jean Bousquet  Oliver Pfaar  Alkis Togias  Holger J. Schünemann  Ignacio Ansotegui  Nikolaos G. Papadopoulos  Ioanna Tsiligianni  Ioana Agache  Josep M. Anto  Claus Bachert  Anna Bedbrook  Karl‐Christian Bergmann  Sinthia Bosnic‐Anticevich  Isabelle Bosse  Jan Brozek  Moises A. Calderon  Giorgio W. Canonica  Luigi Caraballo  Victoria Cardona  Thomas Casale  Lorenzo Cecchi  Derek Chu  Elisio Costa  Alvaro A. Cruz  Wienczyslawa Czarlewski  Stephen R. Durham  George Du Toit  Mark Dykewicz Motohiro Ebisawa  Jean Luc Fauquert  Montserrat Fernandez‐Rivas  Wytske J. Fokkens  João Fonseca Jean‐François Fontaine  Roy Gerth van Wijk  Tari Haahtela  Susanne Halken  Peter W. Hellings  Despo Ierodiakonou  Tomohisa Iinuma  Juan Carlos Ivancevich  Lars Jacobsen  Marek Jutel  Igor Kaidashev Musa Khaitov  Omer Kalayci  Jörg Kleine Tebbe  Ludger Klimek  Marek L. Kowalski  Piotr Kuna  Violeta Kvedariene  Stefania La Grutta  Désirée Larenas‐Linemann  Susanne Lau  Daniel Laune  Lan Le  Karin Lodrup Carlsen  Olga Lourenço  Hans‐Jørgen Malling  Gert Marien  Enrica Menditto  Gregoire Mercier Joaquim Mullol  Antonella Muraro  Robyn O’Hehir  Yoshitaka Okamoto  Giovanni B. Pajno  Hae‐Sim Park  Petr Panzner  Giovanni Passalacqua  Nhan Pham‐Thi  Graham Roberts  Ruby Pawankar  Christine Rolland  Nelson Rosario  Dermot Ryan  Bolesław Samolinski  Mario Sanchez‐Borges  Glenis Scadding Mohamed H. Shamji  Aziz Sheikh  Gunter J. Sturm  Ana Todo Bom  Sanna Toppila‐Salmi  Maryline Valentin‐Rostan  Arunas Valiulis  Erkka Valovirta  Maria‐Teresa Ventura  Ulrich Wahn  Samantha Walker  Dana Wallace  Susan Waserman  Arzu Yorgancioglu  Torsten Zuberbier  the ARIA Working Group

Abstract
Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence‐based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals.

High occurrence of antihistamine resistance in patients with recurrent idiopathic angioedema

• Letter to the Editor
• Open Access 
Clinical and Translational Allergy

• Zonne L. M. HofmanView ORCID ID profile,
• Nikki van West,
• C. Erik Hack,
• André C. Knulst,
• Coen MaasView ORCID ID profile and
• Heike RöckmannEmail author

Clinical and Translational Allergy20199:35

https://doi.org/10.1186/s13601-019-0274-7

Abstract

Antihistamines are the most prescribed therapy in recurrent idiopathic angioedema, yet little is known about their efficacy. Herein, we report on clinical improvement with antihistamine therapy in 120 patients evaluating angioedema attack frequency. A high incidence (36%) of antihistamine refractory cases was observed.

Attack frequency in relation to antihistamine prophylaxis. Attack frequencies were evaluated at maximum antihistamine dose prescribed (prior to add-on therapy) a box-and-whiskers-plot of attack frequency at first visit (V1) and follow-up (FU) with (+),or without intervention (−), bold line = median, Mann–Whitney and Wilcoxon test were used comparing groups respectively paired samples. b Percentage of patients reporting improvement per maximum dose antihistamines prescribed, improvement was defined as shift into a lower attack frequency group, n = total patients per group, patients with missing data on attack frequency could not be evaluated for improvement (n = 25). c Attack frequency per maximum dose prescribed

Rhinovirus replication and innate immunity in highly differentiated human airway epithelial cells

• Research
• Open Access 
Respiratory Research

• Stephanie M. Warner,
• Shahina Wiehler,
• Aubrey N. Michi and
• David ProudEmail authorView ORCID ID profile

Respiratory Research201920:150

Abstract

Background

Human rhinovirus (HRV) infections are the primary cause of the common cold and are a major trigger for exacerbations of lower airway diseases, such as asthma and chronic obstructive pulmonary diseases. Although human bronchial epithelial cells (HBE) are the natural host for HRV infections, much of our understanding of how HRV replicates and induces host antiviral responses is based on studies using non-airway cell lines (e.g. HeLa cells). The current study examines the replication cycle of HRV, and host cell responses, in highly differentiated cultures of HBE.

Methods

Morphology of highly differentiated human bronchial epithelial cultures. a Histology of HBE cultures showing a pseudostratified morphology with numerous cilia. Goblet cells are shown using Alcian blue staining. b Scanning electron micrograph demonstrating a dense blanket of cilia

Highly differentiated cultures of HBE were exposed to initial infectious doses ranging from 104 to 101 50% tissue culture-infective dose (TCID50) of purified HRV-16, and responses were monitored up to 144 h after infection.