Declaration of Interests:
STS reports a grant of GSK and consultancies for AstraZeneca, ERT, Novartis, Sanofi Pharma and Roche. All these are outside the submitted work. All other authors declare no conflicts of interest.
Word count of the text : 3455/3500.
Word count of the abstract : 249/250.
No. of tables/figures: 3 tables and 3 figures.
Supporting information : Text, 8 figures, 3 tables