High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial

Kara Johnson,1,2 Charlene E McEvoy,3 Sakina Naqvi,1,4 Chris Wendt,1 Ronald A Reilkoff,4,5 Ken M Kunisaki,1 Erin E Wetherbee,1 David Nelson,6 Rabindra Tirouvanziam,7 Dennis E Niewoehner1 1Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, 2Sanford Health, Fargo, ND, 3Pulmonary Section, HealthPartners Research Foundation, St Paul, 4HealthEast Maplewood Clinic, Maplewood, 5Pulmonary Section, University of Minnesota Medical Center, 6Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN, 7Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA 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. Keywords: COPD, chronic bronchitis, N-acetylcysteine&nbsp

High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial

Kara Johnson,1,2 Charlene E McEvoy,3 Sakina Naqvi,1,4 Chris Wendt,1 Ronald A Reilkoff,4,5 Ken M Kunisaki,1 Erin E Wetherbee,1 David Nelson,6 Rabindra Tirouvanziam,7 Dennis E Niewoehner1 1Pulmonary Section, Minneapolis VA Health Care System, Minneapolis, MN, 2Sanford Health, Fargo, ND, 3Pulmonary Section, HealthPartners Research Foundation, St Paul, 4HealthEast Maplewood Clinic, Maplewood, 5Pulmonary Section, University of Minnesota Medical Center, 6Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN, 7Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA 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. Keywords: COPD, chronic bronchitis, N-acetylcysteine&nbsp

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. METHODS: This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). CONCLUSION: Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers