Background Clinical outcomes are worse in patients with COPD and chronic bronchitis. N-acetylcysteine (NAC) is commonly prescribed for such patients but with uncertain clinical benefits. We postulated that oral NAC, at much larger doses than those ordinarily prescribed, would improve clinical outcomes in a subset of patients with COPD and chronic bronchitis. Objective The aim of this study was to determine whether very high-dose NAC would improve respiratory health status in patients with COPD and chronic bronchitis. Methods Patients with COPD and chronic bronchitis were enrolled in a randomized, controlled, double-blinded trial. Patients received oral NAC (1,800 mg) or matching placebo twice daily for 8 weeks in addition to their usual respiratory medications. The primary outcome, respiratory health status, was assessed by changes in the St George’s Respiratory Questionnaire. The effects of NAC on lung function and circulating markers of oxidative stress and inflammation were also evaluated. Results We terminated the study prematurely because new external information suggested the possibility of a safety issue. Of the planned 130 patients, 51 were randomized and 45 (22 in the placebo arm and 23 in the NAC arm) completed the study. There was no statistically significant difference between changes in the St George’s Respiratory Questionnaire total score, comparing NAC to placebo (adjusted mean difference, 0.1 U; 95% CI, −7.8 to 8.18 U; P=0.97). There were also no significant NAC-related improvements in any of the secondary outcomes. Conclusion In this 8-week trial, we were unable to show any clinical benefit from a very high dose of NAC in patients with COPD and chronic bronchitis.

Background: Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. Methods: We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G551D, F508del, and healthy controls were also treated with ivacaftor ex vivo to assess mutation-specific effects. Results: Compared to healthy controls, G551D CF subjects had significantly higher expression of active CD11b on PMNs and of CD63 on monocytes, which were normalized by in vivo ivacaftor treatment. Ex vivo exposure to ivacaftor of blood cells from G551D, but not F508del and healthy subjects, resulted in changes in CXCR2 and CD16 expression on PMNs. Conclusions: In vivo and ex vivo exposure of G551D CF leukocytes to ivacaftor resulted in an altered activation profile, suggesting mutation-specific leukocyte modulation.