The sample size is based on changes in the frequency distribution of AFD towards more patients having more AFD in the 7 days following BAL. Using models outlined in the Study Protocol as exemplars of different effect sizes, we would judge that effect sizes of 0.7 and above would represent an important clinical difference under biomarker-guided care. From this exploration, our power calculation was judged to balance detectable effect size against feasible recruitment, on which basis to detect an effect size of 0.0797, 90 patients are required per study arm. Allowing for a 15% drop out (from non-evaluable data in case of problems running biomarker assays etc), a total sample size of 210 patients are required.