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Notably, two such trials with low dose NAC, 600 mg/day over 3 years demonstrated some efficacy in inhaled corticosteroid (ICS)-nave patients only ( High-dose NAC (1,200 mg/day) showed superior outcomes, improving lung volumes [Forced Vital Capacity (FVC), Residual Volume/ Total Lung Capacity (RV/TLC), Inspiratory Capacity (IC)] and exercise tolerance( 2575% ), reactance at 6 Hz, and resonant frequency over 1 year, while these declined with placebo ( The PANTHEON trial, a large double-blind RCT in GOLD defined COPD patients with severe airflow obstruction and a history of 2 COPD exacerbations in the previous year, found that NAC 600 mg BID reduced exacerbation rates in NAC group (497 acute exacerbations in 482 patients, 1.16 AcEx/pt/yr) versus placebo (641 acute exacerbations in 482 patients, 1.49 AcEx/Pt/yr), p 1 log 10 ) compared to untreated controls (67)