[The star walk test in normal subjects].
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The reproducibility of the 12 minute walking distance (12 MD) was assessed in ten men with chronic airways obstruction, and the 12 MD was used, together with spirometry, transfer factor and three subjective assessments of breathlessness to evaluate the effects on respiratory function of prednisone 30 mg daily given orally in double-blind placebo-controlled fashion for two weeks. Like others, we found the 12 MD reproducible on a single day with a mean variation of 3.1%. Tests performed two weeks apart showed greater variability ranging from 0.2% to 30.9%, (mean 9.1%). During placebo and prednisone therapy the 12 MD and assessments of breathlessness correlated significantly with each other and with TLCO, but not with spirometry. Following steroid therapy there was a significant increase in mean TLCO but no significant change in 12 MD, spirometry or subjective assessments. Changes in 12 MD and TLCO correlated significantly with each other and with changes in subjective assessments. Changes in FEV1 correlated with changes in breathlessness, and also with variability in FEV1 while receiving placebo. Individuals with the greatest changes in 12 MD and FEV1 were those with the greatest variability on placebo. The variability of the 12 MD and FEV1 should be measured in individuals before using these tests to assess response to steroid therapy.
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BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.
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