Table 2.
Type of intervention and primary outcomes evaluated.
| ID | Author | Intervention name | Time (months) | Dose (mg/day) | Via | Main outcome | Intervention | Comparison | P value |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Fowdar [28] | NAC | <6 versus 6 | >600 versus 600 | Oral | Exacerbation: acute worsening of respiratory symptoms resulting in the requirement for further therapy, triggered by bacterial or viral respiratory infection, environmental contaminants, or unknown factors | ∗ 0.85 (0.76–0.96) | 0.006 | |
| 2 | Aytemur [34] | NAC | 1 | 200 | Oral | Symptom improvement: 7-point scale (1 is the worst symptom and 7 is the best state) | 0.62 | 0.31 | 0.96 |
| 3 | Kirkil [43] | Zinc picolinate | 2 | 22 | Oral | Pulmonary function parameters: | |||
| (i) FEV1 (%) | 42.73 (5.83) | 42.93 (2.71) | 0.89 | ||||||
| (ii) FEV1/FVC (%) | 64.26 (7.50) | 64.00 (3.94) | 0.87 | ||||||
|
| |||||||||
| 4 | Tse [33] | NAC | 12 | 1200 | Oral | Exacerbation: presence of two of the following symptoms: increased shortness of breath, increased volume of sputum, and increased purulence of sputum | 0.96/year | 1.71/year | 0.019 |
| 5 | Nadeem [41] | Vitamin E | 2 | 800 UI | Oral | Pulmonary function parameters: | 51.56 (18.84) | 47.14 (20.56) | NR |
| (i) FEV1 | |||||||||
|
| |||||||||
| 6 | Decramer [36] | NAC | 36 | 600 | Oral | Annual reduction in FEV1 (ml) | 54 (6)∗∗ | 47 (6)∗∗ | NR |
| 7 | Schermer [35] | NAC | 36 | 600 | Oral | Annual exacerbation rate | Rate ratio | ||
| (i) Intention to treat | 1.35 | 0.054 | |||||||
| (ii) Per protocol | 1.58 | 0.099 | |||||||
|
| |||||||||
| 8 | Cai [45] | High-fat, low-carb formula | 3 weeks | 237 mL | Oral | Changes in pulmonary function: | 48 (9) | 42 (9) | <0.05 |
| (i) FEV1 | |||||||||
|
| |||||||||
| 9 | Stey [32] | NAC | 1 a 6 | 600 | Oral | Exacerbation prevention | ∗ 1.56 (1.37–1.77) | NR | |
| 10 | Martineau [39] | Vitamin D | 12 | 3 (120.000 UI) | Oral | Time to moderate or severe exacerbation | +0.86 (0.60–1.24) | 0.42 | |
| 11 | Vermeeren [44] | Nutritional support | 8 days | 125 ml (20% protein, 20% fat, 60% energy) | Oral | Change in lung function parameters: | |||
| (i) FEV1 (%) | 5 (6) | 5 (9) | <0.05 | ||||||
| (ii) IVC (%) | 7 (12) | 10 (17) | <0.05 | ||||||
|
| |||||||||
| 12 | Dueholm [38] | NAC | 1 | 8 | Inhaled | Changes in symptoms (score of 0–10) | NR | ||
| (i) Wellness | 0.16 (−1.03; 0.75) | ||||||||
| (ii) Cough | 1.05 (−0.12; 1.36) | ||||||||
| (iii) Dyspnea in the morning | 0.49 (−0.16; 1.19) | ||||||||
| (iv) Dyspnea with exercise | 0.55 (−0.09; 1.39) | ||||||||
| (v) Booger | 0.50 (−0.29; 1.11) | ||||||||
| Expectoration: | |||||||||
| (i) Quantity | 0.15 (−0.39; 0.93) | ||||||||
| (ii) Viscosity | 0.14 (−0.77, 0.64) | ||||||||
| (iii) Difficulty | 0.23 (−1.18, 0.88) | ||||||||
|
| |||||||||
| 13 | Parr [37] | NAC | 12 | 200 | Oral | Number of exacerbations (patients/year) | 2.2 | 2.5 | NR |
| 14 | Jolliffe [40] | Vitamin D | . | . | Oral | Moderate or severe exacerbation | 0.94 (IC95% 0.78; 1.13) | 0.52 | |
| 15 | Rogliani [31] | Erdosteine, | 6 ECA: 13 | E: 600 | Oral | Acute exacerbation: | <0.001 | ||
| NAC | 1 ECA: 8 | C: 1500 | (i) General | 0.61 (0.51–0.82)∗ | |||||
| Carbocysteine | N: 1200 | (ii) Erdosteine, | 0.76 (0.66–0.87)∗ | ||||||
| (iii) NAC | 0.68 (0.49–0.93)∗ | ||||||||
| (iv) Carbocysteine | 0.44 (0.24–0.82)∗ | ||||||||
|
| |||||||||
| 16 | Meng-Chun [47] | Oligomeric proanthocyanidins | 2 | 150 | Oral | Pulmonary function parameters: | NR | ||
| (i) FEV1 (%) | 65.85 (7.97) | 69.71 (6.38) | |||||||
| (ii) FVC (%) | 43.92 (5.39) | 46.29 (4.56) | |||||||
| (iii) FEV1/FVC (%) | 53.54 (4.79) | 52.79 (4.43) | |||||||
| (iv) PEFR (%) | 45.54 (4.49) | 45.93 (4.12) | |||||||
|
| |||||||||
| 17 | Panahi [46] | Chlorella vulgaris extract | 2 | 2700 | Oral | Magnitude of change in oxidative stress biomarkers: | |||
| (i) MDA | −2.03 (0.86) | −0.60 (1.47) | 0.025 | ||||||
| (ii) VIT E | 2.78 (15.88) | 0.05 (0.25) | <0.001 | ||||||
| (iii) VIT C | 0.46 (0.34) | −0.04 (0.20) | <0.001 | ||||||
| (iv) GSH | 9.37 (2.34) | 2.60 (5.20) | <0.001 | ||||||
| (v) GPx | 2.26 (0.44) | 0.15 (1.12) | <0.001 | ||||||
| (Vi) CAT | 10.51 (5.01) | −1.73 (5.26) | <0.001 | ||||||
| (vii) SOD | 1.01 (0.56) | 0.60 (0.78) | 0.011 | ||||||
| (viii) TAL | 0.30 (0.24) | 0.20 (0.29) | 0.104 | ||||||
|
| |||||||||
| 18 | Matos [42] | Melatonin | 3 | 3 | Oral | Oxidative lung stress: isoprostane-8 (average difference) | 7.708 | −0.613 | NR |
| 19 | Cerdá [48] | Granada juice | 1.2 | 400 ml | Oral | Pulmonary function parameters: | NR | ||
| (i) FEV1 | 1.38 (0.61) | 0.91 (0.92) | |||||||
| (ii) FVC | 2.94 (0.76) | 2.03 (0.39) | |||||||
| (iii) FEV1/FVC | 45.60 (13.28) | 44.1 (0.44) | |||||||
| (iv) Pa02 | 72.19 (8.70) | 71.67 (0.97) | |||||||
| (v) PC02 | 40.35 (4.66) | 42.50 (0.95) | |||||||
NAC : N-Acetylcysteine; ∗ relative risk (95% CI); +hazard ratio (95% CI); ∗∗ average difference (standard error); rate ratio: number of times per year that patients treated with NAC have exacerbations compared to placebo; MDA: malondialdehyde; vit E: vitamin E; vit C: vitamin C; GSH: glutathione; GPX: glutathione peroxidase; CAT: catalase; SOD: superoxide dismutase; TAS: total antioxidant status.