Twitter notes from Peter Barnes' lecture about asthma therapy

Peter Barnes is Professor of Thoracic Medicine and Head of Airway Disease at the National Heart and Lung Institute and Honorary Consultant Physician at Royal Brompton Hospital, London. He has published over 1000 peer-review papers on asthma, COPD and related topics and has edited over 40 books. He is also amongst the top 50 most highly cited researchers in the world and has been the most highly cited clinical scientist in the UK and the most highly cited respiratory researcher in the world over the last 20 years.

These are some of my notes from his recent lecture on asthma therapy to the Nebraska Allergy Society, posted on Twitter via text messages:

• Peter Barnes believes formoterol is a superior drug to salmeterol, unique for asthma therapy, provides quick relief, better compliance. He thinks the future of asthma therapy is SMART - Symbicort, regular use plus prn, he says they don't use Advair anymore.
  
  
• Proposed triple therapy for asthma - ICS/LABA/LAMA (long acting muscarinic antagonist). Unfortunately LAMA doesn't work that well in asthma.
  
  
• Peter Barnes: anti-IL4/IL13 didn't work for asthma, anti-IL5 is an orphan drug for rare asthma subtype - likely less than 0.01% of patients.
  
  
• New asthma therapy? - anti-TSLP (IL7 family) - works in mice.
  
  
• "We used to think the mast cell is the key cell in asthma, then chased the eosinophil, now we are back to the mast cell."
  
  
• Only 60 patients in the UK treated with omalizumab (Xolair), difficult to predict who will respond.
  
  
• Peter Barnes: PDE4 inhibitor as effective as ICS but use limited by nausea at higher doses. Doesn't work as inhalation.
  
  
• Patients like a pill for asthma - the reason behind Singulair's commercial success (it doesn't work according to Peter Barnes).

Interleukin-7 receptor (IL7R)

Interleukin 7 receptor (IL7R), also known as CD127 (Cluster of Differentiation 127), is a type I cytokine receptor. Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands.

Type I cytokine receptors are mediated through JAK/STAT and bind: IL-2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, GM-CSF.


Key steps of the JAK-STAT pathway. Image source: Wikpedia, public domain.

IL7R plays a critical role in the V(D)J recombination during lymphocyte development. A defect in IL-7RA leads to SCID (T-/B+/NK+).

Thymic stromal lymphopoietin (TSLP)

Thymic stromal lymphopoietin (TSLP) signals through a heterodimeric receptor complex composed of the TSLP receptor and the IL-7R alpha chain. Some researchers have classified TSLP as a "master regulator" of the Th2 response due to overexpression of the cytokine in pulmonary tissue and skin cells result in Th2-induced asthma and dermatitis.

TSLP is produced mainly by non-hematopoietic cells as fibroblasts, epithelial cells and different types of stromal cells.

Anti-TSLP is a potential new therapeutic target in asthma.

References:
Professor Peter J Barnes. Imperial College London.

The most influential respiratory researcher: Peter Barnes with over 26,000 citations http://goo.gl/HZh93
CD127, IL-7 receptor alpha chain

Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma http://goo.gl/c0vzJ
Single inhaler therapy in asthma (SMART) linked to poor day-to-day control of symptoms and increasing inflammation. Clin Exp Allergy. 2012 Jan 18.