Table 3.
Type of intervention and secondary outcomes evaluated.
| ID | Author | Intervention | Secondary outcomes | Intervention | Comparison | P value |
|---|---|---|---|---|---|---|
| 1 | Fowdar [28] | NAC | Hospital admissions (absolute frequency): 3 studies | 37/50 | 55/50 | NR |
| 26/52 | 45/56 | |||||
| 33/482 | 36/482 | |||||
| Duration of exacerbation (days): 2 studies | 17.2 | 23.7 | NR | |||
| 14.8 | 19.2 | <0.0001 | ||||
|
| ||||||
| 2 | Aytemur [34] | NAC | Arterial Gases: | |||
| (i) Pa02 (mmHg) | 70.5 (15.0) | 68.7 (12.4) | 0.777 | |||
| (ii) PaC02 (mmHg) | 43.5 (9.1) | 44.5 (5.3) | NR | |||
| (iii) Sa02 (%) | 92.9 (4.5) | 92.6 (4.5) | 0.979 | |||
| FEV1 (ml) | 1239 (543) | 1180 (535) | 0.076 | |||
| Hospital stay (days) | 10.5 (3.8) | 9.8 (3.0) | 0.52 | |||
| Number of exacerbations at 6 months | 1.1 (1.3) | 1.0 (1.4) | 0.788 | |||
| Time to exacerbation (days) | 50.4 (66.2) | 22.7 (27.6) | 0.347 | |||
| Number of hospitalizations at six months of follow-up | 0.9 (1.1) | 0.6 (0.9) | 0.424 | |||
| Time to hospital admission (days) | 45.6 (67.2) | 24.6 (41.5) | 0.373 | |||
|
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| 3 | Kirkil [43] | Zinc | Serum levels: baseline versus postsupplementation | |||
| (i) MDA (nmol/mL) | 0.51 (0.15) | 0.46 (0.38) | 0.061 | |||
| (ii) SOD (U/mL) | 0.16 (0.02) | 0.18 (0.01) | 0.029 | |||
| (iii) CAT (k/mL) | 14.79 (3.03) | 16.27 (1.10) | 0.523 | |||
| (iv) Zinc (mg/dL) | 77.33 (4.29) | 87.36 (4.96) | <0.001 | |||
|
| ||||||
| 4 | Tse [33] | NAC | Time to exacerbation (days) | 261.5 (18.4) | 239.5 (17.9) | 0.17 |
| Exacerbation-free patients | 53.8% | 37.5% | 0.088 | |||
|
| ||||||
| 5 | Nadeem [41] | Vitamin E | Indicators of Oxidative Stress: | |||
| (i) Generation of superoxide leukocytes (nm O2¯ produced/15 min/2.5 × 106 cells) | 16.54 (7.77) | 14.6 (8.53) | NR | |||
| (ii) Plasma peroxidized lipids (μM/l) | 3.79 (0.94) | 3.93 (0.99) | ||||
| (iii) Total plasma protein carbonyls (nm/mg protein) | 1.14 (0.26) | 1.16 (0.25) | ||||
| (iv) Total plasma proteins sulfhydryls (nm/l) | 0.53 (0.09) | 0.51 (0.08) | ||||
| (v) Total nitrates and nitrites (μM/l) | 69.09 (35.51) | 68.8 (39.64) | ||||
| Antioxidant status indicators: | NR | |||||
| (i) Red cell superoxide dismutase (U/g Hb) | 2040.4 (783.7) | 2126.1 (831.4) | ||||
| (ii) Red cell catalase (U/g Hb) | 3382.1 (1012.4) | 3005.1 (1062.9) | ||||
| (iii) Total blood glutathione (nM) | 1.21 (0.65) | 0.78 (0.57) | ||||
| (iv) Red cell glutathione peroxidase (μM oxidized NADPH/min/g Hb) | 50.6 (13.5) | 47.3 (13.2) | ||||
| (v) Plasma glutathione peroxidase (oxidized nM NADPH/min/ml) | 169.7 (73.8) | 184.1 (55.8) | ||||
| (vi) Total plasma antioxidant power (μM) | 554.2 (48) | 650.01 (183.3) | ||||
|
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| 6 | Decramer [36] | NAC | Probability of exacerbations per year | 0.99∗ (0.89–1.10) | 0.85 | |
| Probability of exacerbations per year in patients without inhaled corticosteroids | 0.79∗ (0.63–0.98) | 0.04 | ||||
| EuroQoL-5D (first year) | 0·018 (–0·015; 0·05) | 0·037 (0·004; 0·069) | 0.414 | |||
| EuroQoL-5D (after the first year) | –0·02 (–0·034; 0·005) | –0·02 (–0·034; –0·004) | 0.965 | |||
| St. George's respiratory questionnaire (1st year) | –3.76 (–5.55; –1.98) | –4.95 (–6.74; –3.16) | 0.358 | |||
| St. George's respiratory questionnaire (annual decrease) | 1.45 (0.52; 2.38) | 1.24 (0.28; 2.21) | 0.763 | |||
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| ||||||
| 7 | Schermer [35] | NAC | Quality of life (total score) | |||
| (i) Score chronic respiratory questionnaire CRQ | <0.5 | <0.5 | 0.306 | |||
| Pulmonary function parameters (at three years): | −60 (5.4)∗∗ | NR | ||||
| (i) FEV1 (mL) after BD | −64 (5.4)∗∗ | −62 (7.1)∗∗ | ||||
| (ii) Tight | −60 (7.5)∗∗ | |||||
| (iii) Per protocol | −65 (9.4)∗∗ | |||||
| (iv) FVC (mL) after BD | −79 (9.5)∗∗ | −57 (13.1)∗∗ | ||||
| (v) Tight | −51 (13.9)∗∗ | |||||
|
| ||||||
| 8 | Cai [45] | High-fat, low-carb formula | Arterial gases: | NR | ||
| (i) PH | 7.38 (0.21) | 7.37 (0.21) | ||||
| (ii) Pc02 (mm Hg) | 42 (3) | 45 (3) | ||||
| (iii) Po2 (mm Hg) | 79 (4) | 71 (6) | ||||
|
| ||||||
| 9 | Stey [32] | NAC | Decrease in symptoms (cough, mucopurulent sputum, and dyspnea) | 1.78∗ (1.54–2.05) | NR | |
| 10 | Martineau [39] | Vitamin D | Time it takes for the first upper respiratory infection to appear | 0.95∗ (0.69–1.31) | 0.75 | |
| 11 | Vermeeren [44] | Nutritional support | Changes in symptoms (score): | |||
| (i) Dyspnea at rest | −3.8 (2.5) | −4.3 (3.2) | <0.05 | |||
| (ii) Dyspnea while eating | −4.2 (2.5) | −4.7 (3.3) | <0.05 | |||
| (iii) Loss of appetite | −2.7 (3.2) | −2.6 (2.9) | <0.05 | |||
| (iv) Early satiety | −3.2 (3.3) | −2.5 (3.3) | <0.05 | |||
| (v) Borborygmus | −2.4 (3.4) | −3.0 (2.8) | <0.05 | |||
| (vi) Fatigue | −4.2 (3.7) | −3.9 (3.5) | <0.05 | |||
|
| ||||||
| 12 | Dueholm [38] | NAC | Pulmonary function: | |||
| (i) FEV1 | 1.9 (0.18) | 2.0 (0.13) | NS | |||
| (ii) FVC | 3.0 (0.21) | 2.9 (0.18) | ||||
| (iii) PEFR | 356.7 (29.64) | 354.6 (25.07) | ||||
| Number of exacerbations | 9 | 7 | NR | |||
|
| ||||||
| 14 | Jolliffe [40] | Vitamin D | Time to first exacerbation (3 studies) | 0.93∗ (0.74–1.17) | 0.53 | |
| % FEV1 at the end of the study (3 studies) | 54.9 (21.0) | 54.9 (21.9) | 0.16 | |||
| % HRV at the end of the study (3 studies) | 88.8 (20.0) | 89.9 (21.8) | 0.49 | |||
|
| ||||||
| 15 | Rogliani [31] | Erdosteine | Risk of at least one exacerbation | NR | ||
| (i) General | 0.90∗ (0.83–0.96) | |||||
| (ii) Erdosteine | 0.82∗ (0.70–0.95) | |||||
| (iii) NAC | 0.88∗ (0.74–1.05) | |||||
| (iv) Carbocysteine | 0.94∗ (0.83–1.07) | |||||
| NAC | Duration of exacerbation (days) | NR | ||||
| (i) General | −2.63 (−4.03; –1.23) | |||||
| (ii) Erdosteine | −2.04 (−3.51; –0.57) | |||||
| (iii) NAC | −3.56 (−5.46; –1.66) | |||||
| Carbocysteine | Risk of hospitalization due to exacerbation | NR | ||||
| (i) General | 0.69∗ (0.52–0.91) | |||||
| (ii) Erdosteine | 0.56∗ (0.33–0.94) | |||||
| (iii) NAC | 0.75∗ (0.51–1.10) | |||||
|
| ||||||
| 16 | Meng-Chun [47] | Oligomeric proanthocyanidins | Plasma concentration of oxidative markers: MDA (nmol/ml) | 5.87 (0.27) | 7.95 (0.41) | NR |
| (i) SOD (U/g protein) | 2.70 (0.45) | 5.37 (0.87) | ||||
| (ii) Catalase (U/g protein) | 13.42 (1.25) | 16.51 (1.65) | ||||
| (iii) GSH–PX (U/g protein) | 0.14 (0.01) | 0.19 (0.03) | ||||
| Plasma lipids: | NR | |||||
| (i) Total cholesterol (mg/dl) | 198 (13) | 202 (9) | ||||
| (ii) Triglycerides (mg/dl) | 114 (20) | 125 (21) | ||||
| (iii) HDL (mg/dl) | 59 (4) | 47 (4) | ||||
| (iv) LDL (mg/dl) | 120 (12) | 126 (7) | ||||
|
| ||||||
| 18 | Matos [42] | Melatonin | IL-8 (pg/mL) | 2.24 (0.98) | 2.41 (0.82) | NR |
| FVC (L) | 2.76 (0.67) | 2.90 (0.70) | ||||
| FEV1 (L) | 1.46 (0.54) | 1.44 (0.46) | ||||
| MRC score | 1.56 (1.38) | 1.56 (1.38) | ||||
| 6-MWT (m) | 391 (56) | 389 (76) | ||||
NAC : N-Acetylcysteine; ∗ hazard ratio (95% CI); ∗∗ average (standard error); IVC : inspiratory vital capacity; GSH-Px : glutathione peroxidase; FVC : forced vital capacity; 6-MWT: 6-minute walk test. ∗∗ Measurements at the time of hospital discharge. NS : not significant; NR : no report; MDA : plasma malondialdehyde; SOD : superoxide dismutase; CAT : catalase.