Table I.
Characteristics of the studies included.
| Sample size | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| First author (year) | Type of study | Population (n) | NAC | Control | Duration | Outcome | Quality score | NAC regimen | Complete intervention | (Refs.) |
| Bando (2010) | Case-control | 25 | 14 | 11 | 12 months | ABDFH | Concealment: No; ITT: Yes; Blinding: No (score, 6) | Daily dose: 704.8 mg Route: inhaled | Intervention: NAC (352.4 mg, bid) Control: Without therapy | (18) |
| Behr (2016) | RCT | 123 | 61 | 62 | 24 weeks | ABDGH | Concealment: Yes; ITT: Yes Blinding: Double (score, 12) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + pirfenidone (1,602–2,043 mg/d) Control: Pirfenidone (1,602–2,043 mg/d) | (19) |
| Demedts (2005) | RCT | 155 | 80 | 75 | 12 weeks | BCDEH | Concealment: Yes; ITT: Yes; Blinding: Double (score, 12) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) Control: Placebo | (13) |
| Fu (2015) | RCT | 30 | 15 | 15 | 6 months | E | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance) Control: Prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance) | (26) |
| Homma (2012) | RCT | 100 | 51 | 49 | 48 weeks | AB | Concealment: No; ITT, Yes; Blinding: No (score, 10) | Daily dose: 704.8 mg Route: Inhaled | Intervention: NAC (352.4 mg, bid) Control: Without therapy | (14) |
| Huang (2015) | RCT | 74 | 37 | 37 | 6 months | ABCF | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance) Control: Prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance) | (27) |
| Jiang (2009) | RCT | 26 | 13 | 13 | 12 weeks | ACF | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + methyprednisolone (0.4 mg/kg/d) Control: Methyprednisolone (0.4 mg/kg/d) | (28) |
| Jiang (2008) | RCT | 20 | 12 | 8 | 12 weeks | DF | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 4 weeks, 0.125 mg/kg/d for maintenance) Control: (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 4 weeks, 0.125 mg/kg/d for maintenance) | (29) |
| Liu (2016) | RCT | 116 | 58 | 58 | 6 months | CEF | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 1 month; 0.25 mg/kg/d for 2 months; 0.125 mg/kg/d for 3 months) Control: Prednisone (0.5 mg/kg/d for 1 month; 0.25 mg/kg/d for 2 months; 0.125 mg/kg/d for 3 months) + cyclophosphamide (25–150 mg/d) | (30) |
| Liu (2015) | RCT | 80 | 40 | 40 | 3 months | ABCF | Concealment: No; ITT: No; Blinding: No (score, 8) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + budesonide (1 mg, tid for 4 weeks; 1 mg, bid for 8 weeks) Control: Budesonide (1 mg, tid for 4 weeks; 1 mg, bid for 8 weeks) | (31) |
| Long (2011) | RCT | 20 | 10 | 10 | 6 months | HF | Concealment: No; ITT: Yes, Blinding: No (score, 8) | Daily dose: 600 mg Route: Po | Intervention: NAC 600 mg, tiw + prednisone (0.5 mg/kg/d) + γ-IFN (200 U, subcutaneous injection, tiw) Control: Prednisone (0.5 mg/kg/d) + γ-IFN (200 U, subcutaneous injection, tiw) | (32) |
| Lu (2013) | RCT | 62 | 32 | 30 | 6 months | BDEF | Concealment: No; ITT: No; Blinding: No (score, 8) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d maintenance) Control: Prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d maintenance) | (33) |
| Luo (2006) | RCT | 40 | 20 | 20 | 12 months | CEH | Concealment: No; ITT: Yes; Blinding: No (score, 8) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (30–45 mg/d) Control: Prednisone (30–45 mg/d) | (34) |
| Martinez (2014) | RCT | 264 | 133 | 131 | 60 weeks | BGH | Concealment: Yes; ITT: Yes; Blinding: Double (score, 11) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) Control: Placebo | (20) |
| Nan (2007) | RCT | 40 | 20 | 20 | 12 months | ACF | Concealment: No; ITT: No; Blinding: No (score, 6) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 1 month; 0.4 mg/kg/d for 1 month, 0.3 mg/kg/d for 1 month; 10 mg, qd for maintenance) + azathioprine (2 mg/kg/d) Control: Prednisone (0.5 mg/kg/d for 1 month; 0.4 mg/kg/d for 1 month, 0.3 mg/kg/d for 1 month; 10 mg, qd for maintenance) + azathioprine (2 mg/kg/d) | (35) |
| Sakamoto (2013) | Retrospective study | 18 | 11 | 7 | 6 months | AH | Concealment: No; ITT: No; Blinding: No (score, 6) | Daily dose: 704.8 mg Route: Inhaled | Intervention: NAC (352.4 mg, bid) + pirfenidone (1,200–1,800 mg/d) Control: Pirfenidone (1,200–1,800 mg/d) | (15) |
| Sakamoto (2015) | Case-control | 34 | 24 | 10 | 12 months | B | Concealment: No; ITT: No; Blinding: No (score, 8) | Daily dose: 704.8 mg Route: Inhaled | Intervention: NAC (352.4 mg, bid) + pirfenidone (1,200–1,800 mg/d) Control: Pirfenidone (1,200–1,800 mg/d) | (16) |
| Tominoka (2005) | RCT | 30 | 15 | 15 | 12 months | GH | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 352 mg Route: Inhaled | Intervention: NAC (352 mg/d) Control: Bromhexine hydrochloride (4 mg/d) | (17) |
| Wang (2015) | RCT | 42 | 21 | 21 | 6 months | BCEF | Concealment: No; ITT: No; Blinding: No (score, 7) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 4 weeks; 0.125 mg/kg/d for maintenance Control: Prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 4 weeks; 0.125 mg/kg/d for maintenance | (36) |
| Yang (2008) | RCT | 32 | 17 | 15 | 12 weeks | ABCF | Concealment: No; ITT: No; Blinding: No (score, 6) | Daily dose: 1,800 mg Route: Po | Intervention: NAC (600 mg, tid) Control: Prednisone (0.5 mg/kg/d) | (37) |
| Zhu (2009) | RCT | 23 | 11 | 12 | 6 months | BDFH | Concealment: No; ITT: Yes; Blinding: No (score, 8) | Daily dose: 1,200 mg Route: Po | Intervention: NAC (600 mg, tid) + prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance Control: Prednisone (0.5 mg/kg/d for 4 weeks; 0.25 mg/kg/d for 8 weeks; 0.125 mg/kg/d for maintenance | (38) |
Outcomes: A, FVC; B, adverse events; C, DLCO; D, DLCO%; E, VC; F, PaO2; G, 6MWT; H, mortality. RCT, randomized controlled trial; DLCO, diffusing capacity for carbon monoxide; DLCO%, percentage predicted DLCO; VC, vital capacity; PaO2, partial arterial oxygen pressure; 6MWT, 6-minute walking distance test; ITT, intention to treat; bid, twice a day; n, number of patients; IFN, interferon; Po, Per Os; qd, once a day; tid, three times a day; tiw, three times a week; d, day; NAC, N-acetylcysteine.