N-Acetylcysteine Reduces the Exacerbation Rate in Patients with Moderate to Severe COPD

Abstract

Objective: This study was performed to confirm the efficacy of a 6-month therapy with a formulation of N-acetylcysteine (NAC; 600 mg/day p.o.) on frequency and severity of exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). Methods: One hundred sixty-nine patients attending five Italian centres were recruited in an open, randomized, controlled study. The patients were randomly allocated to standard therapy plus NAC 600 mg once a day or standard therapy alone over a 6-month period. At baseline, medical history was evaluated, and physical examination was performed; occurrence and severity of exacerbations and side effects of NAC were analyzed after 3 and 6 months. Results: The results showed a decreased number of exacerbations (by 41%) in the group of patients treated with NAC and standard treatment: 46 patients had at least one exacerbation as compared with 63 patients of the group treated with standard therapy alone. Also the number of the patients with two or more exacerbations was lower in the NAC group (26%) than in the standard-therapy group (49%). The number of sick days was less (82) in the NAC group as compared with the standard-therapy group (155). There was a small but significant improvement in FEV₁ and MEF₅₀ in the NAC group. NAC once a day was well tolerated. There were no differences in the number of side effects reported in both groups. Conclusions: These data confirm results of previous studies which reported a reduction in the number of exacerbations in patients having moderate to severe COPD treated with the antioxidant NAC. Further, the once-daily formulation is well tolerated and is likely to improve patient compliance with the prescribed regimen.

Influence ofN-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

“…Three studies used high-dose NAC [1,19,20], nine used low-dose NAC [3, [21][22][23][24][25][26][27][28], and one investigated both low-and high-dose NAC [29]. Seven RCTs in which COPD patients were enrolled using PFT in agreement with ATS/ERS or GOLD recommendations were used for the subgroup analysis [1,3,20,22,24,26,27].…”

“…Three studies used high-dose NAC [1,19,20], nine used low-dose NAC [3, [21][22][23][24][25][26][27][28], and one investigated both low-and high-dose NAC [29]. Seven RCTs in which COPD patients were enrolled using PFT in agreement with ATS/ERS or GOLD recommendations were used for the subgroup analysis [1,3,20,22,24,26,27]. Although the study carried out by the British Thoracic Society Research Committee in 1985 [22] was antecedent to both ATS/ERS and GOLD positions, we added it to those RCTs in which COPD patients were enrolled in agreement with ATS/ERS or GOLD statements [8] because, in that study, FEV1 <50% pred and FEV1/FVC<70% pred were specified as PFT outcomes in the inclusion criteria.…”

Effect of N-acetyl-l-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis

“…N-Acetylcysteine (NAC) is able to expand natural antioxidant defense by increasing intracellular reduced gluthatione (GSH) concentration [18,19] and it has been proposed as an antioxidant therapy in respiratory distress syndromes [20]. Effectiveness of NAC in reducing the exacerbation of severe chronic obstructive pulmonary disease has been documented [21] and, more recently, in SSc, NAC intravenous administration has been shown to reduce significantly the number of Raynaud's phenomenon attacks [22]. In an early report, the effect of NAC (administered for 5 days) on the O À 2 anion production of rat alveolar macrophages and human peripheral neutrophiles was evaluated [23].…”

COPD: new treatment strategies

“…[21][22][23] A large multicentre trial of NAC in COPD showed no effect on exacerbation frequency or decline in FEV 1 , 24 but in a subgroup of patients not treated with ICS, NAC did show a reduction in exacerbation frequency and reduced hyperinflation.…”