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First, referring to the Tie-COPD study and PANTHEON study 9,14 , we calculated the sample size using Poisson regression analysis to detect a difference of 0.23 per patient-year between the N -acetylcysteine group (0.27 per patient-year) and the placebo group (0.50 per patient-year) in the annual rate of exacerbations, with a two-sided significance level of 5% and a power of 90% based on an anticipated withdrawal rate of 35%

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