Table 2.
Clinical trials demonstrating effects of NAC in cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), bronchial asthma, and idiopathic pulmonary fibrosis (IPF).
| Diagnosis | No. of Patients | Treatment | Outcomes in NAC-Treated Patients | Study |
|---|---|---|---|---|
| CF | 21 in total (11 low-dose NAC, 10 high-dose NAC) | Oral NAC (700 mg daily or 2800 mg daily p.o.), for 12 weeks | High-dose NAC well-tolerated, trend to ↑ extracellular GSH | [100] |
| CF | 22 in total (10 in study 1, 12 in study 2) | Inhalational NAC: Study 1: from 2 (4 mg) to 8 puffs (16 mg) of NAC, or 12 puffs (24 mg) of NAC for 5 days; Study 2: single dose 12 puffs, 24 h monitoring | Study 1: dose-dependent ↓ in sputum viscoelasticity, ↓ in sputum solids; Study 2: ↓ mucus rigidity, max. at 4 h | [101] |
| CF | 21 in total (11 NAC, 10 control) | Oral NAC (2400 mg/day in 2 doses), for 30 days | ↓ oxidized vit. C, ↑ levels of vit. C, slight improvement in lung function | [102] |
| CF | 70 in total (36 NAC, 34 placebo) | Oral NAC (900 mg, 3 times a day) for 24 weeks | Stable lung function, but no effect on neutrophilic inflammation | [103] |
| CF | 5 in total | Inhalational NAC (20%, 1.27 M), 90 min observation | No effect on mucus properties | [99] |
| COPD | 50 in total (25 NAC, 25 placebo) (ISRCTN21676344) |
Oral NAC (600 mg, twice daily), for 7 days (addition to corticosteroids and bronchodilators) | No effect on lung functions or median length of stay in hospital | [121] |
| COPD | 523 in total (256 NAC, 267 placebo) (BRONCUS trial) | Oral NAC (600 mg/day), patients followed for 3 years | No prevention of deterioration in lung functions, no prevention of exacerbations | [122] |
| COPD | 24 in total (12 NAC, 12 placebo) (NCT00476736) |
Oral NAC (1200 mg/day), for 6 weeks | Beneficial effect on physical performance | [123] |
| COPD | 120 in total (58 NAC, 62 placebo) (HIACE trial, NCT01136239) |
Oral NAC (600 mg bid or placebo after 4-week run-in), for 1 year | Enhanced small AW function, ↓ exacerbation frequency | [7] |
| COPD | 1006 in total (504 NAC, 502 placebo) (PANTHEON trial, ChiCTR-TRC-09000460) | Oral NAC (600 mg, twice daily), for 1 year | Prevention of acute exacerbations | [8] |
| COPD/chronic bronchitis | 45 in total (23 NAC, 22 placebo) (NCT01599884) | Oral NAC (1800 mg twice daily), for 8 weeks | No clinical benefit, study prematurely terminated | [20] |
| COPD | 100 in total (50 NAC, 50 placebo) | Oral NAC (900 mg twice daily), for 3 months | Absence of clinical improvement | [124] |
| COPD | 121 in total (60 NAC, 61 control) | Oral NAC (0.2 g × 10 bags, 0.4 g each time, 3 times/day), for 6 months | ↑ proportion of Treg in CD4+ T cells and ↓ Th17/Treg ratio | [125] |
| Asthma | 25 in total | Oral NAC (200 mg, 3 times daily), for 9 weeks | No effect on spirometric, lung mechanics or gas exchange variables, or frequency of clinical symptoms | [144] |
| Asthma | 50 in total (25 NAC, 25 placebo) | Oral NAC (600 mg/day), for 5 days | No effect on clinical symptoms | [145] |
| IPF | 14 in total (8 NAC, 6 controls) | Intravenous NAC (600 mg, 1800 mg and 4800 mg), in weekly intervals | ↑ GSH in low and moderate dose in IPF patients, but no effect on GSH in controls, no adverse effects | [25] |
| IPF | 31 in total (17 NAC, 14 controls) | Oral NAC (600 mg, 3 times/day), for 5 days | ↑ GSH in BALF/ELF, treatment well-tolerated | [166] |
| IPF | 18 in total | Oral NAC (600 mg, 3 times/daily), for 12 weeks | ↑ GSH in BALF/ELF, ↓ methionine sulfoxide content of BALF proteins, improved lung functions | [167] |
| IPF | 76 in total (38 NAC, 38 controls) | Inhalational NAC (352.4 mg, twice daily), observation for 48 weeks | No differences in lung functions | [168] |
| IPF | 28 in total | Inhalational NAC (352.4 mg, twice daily), observation for 26 weeks | Prevented a ↓ in FVC in mild-to moderate IPF, better effect in more severe IPF | [169] |
| IPF | 22 in total | Inhalational NAC (352.4 mg, twice daily), observation for 12 months | Prevented ↓ in FVC, ↓ oxidative imbalance, better effect in more severe oxidative stress | [170] |
Abbreviations: AW: airway, BALF: bronchoalveolar lavage fluid, CF: cystic fibrosis, COPD: chronic obstructive pulmonary disease, ELF: epithelial lining fluid, FVC: forced vital capacity, GSH: glutathione, IPF: idiopathic pulmonary fibrosis, NAC: N-acetylcysteine, ↑: increased, ↓: decreased.