Background
Trials | Usage of GM-CSF | Maximum dose of GM-CSF | Medication timea | Effective rate | Yearb |
---|---|---|---|---|---|
Seymour et al. [15] | subcutaneous injection | 5 μg/kg/day | 300 days | 100% (n = 1) | 1996 |
Kavuru et al. [16] | subcutaneous injection | 9μg/kg/day | 12 weeks | 75% (n = 4) | 2000 |
Seymour et al [17] | subcutaneous injection | 20μg/kg/d | 6–12 weeks | 43%(n = 14) | 2001 |
Bonfield et al. [18] | subcutaneous injection | 18 μg/kg/day | 12–48 weeks | 55% (n = 11) | 2002 |
Tazawa et al. [19] | inhalation therapy | 250 μg/day; every other week | 24 weeks | 100% (n = 3) | 2005 |
Venkateshiah et al. [20] | subcutaneous injection | 18 μg/kg/day | 12–52 weeks | 48% (n = 21) | 2006 |
Wylam et al. [21] | inhalation therapy | 500ugbid week-on, week-off | 3–68 weeks | 92%(n = 12) | 2006 |
Tazawa et al. [22] | inhalation therap | 250 μg/day d1-d8, d9-d14 no use of drugs × 6 cycles | 24 weeks | 62% (n = 39) | 2010 |
Spyros et al. [23] | inhalation therapy | 250μg qd 4 days-on, 4 days-off | 14–65 weeks | 100%(n = 6) | 2014 |
Tazawa et al. [24] | inhalation therapy | (125 μg bid d1-d8, d9-d14 no use of drugs × 6 cycles) + (125 μg qd d1-d4,d5-d14 no use of drugs× 6 cycles) | 24 weeks | 66%(n = 35 | 2014 |
Materials and methods
Inclusion and exclusion criteria
Drug administration and evaluation scheme
Evaluation of efficacy and safety
Evaluation indexes of efficacy
□ | 0 point | no paving stone signs |
□ | 1 point | paving stone signs less than 5% |
□ | 2 points | 5–24% of paving stone signs |
□ | 3 points | 25–49% of paving stone signs |
□ | 4 points | 50–74% of paving stone signs |
□ | 5 points | paving stone signs more than≥75% |
Polypnea Or dyspnea | □1 point Dyspnea only when exerting themselves. |
□2 points Shortness of breath when walking fast on flat ground or climbing small slopes on foot. | |
□3 points Because of shortness of breath, walking on flat ground is slower than that of their peers or requires stopping to rest. | |
□4 points Stop to catch breath after walking on flat ground for about 100 m or a few minutes | |
□5 points Severe dyspnea prevents the patient from leaving his home or dyspnea while dressing or undressing. | |
cough | □0 point No cough during the day; no cough at night. |
□1 point There are occasional short coughs in the daytime; temporary coughs or occasional coughs when sleeping at night. | |
□2 points Frequent cough during the day slightly affects daily activities; cough slightly affects sleep at night. | |
□3 points Frequent cough during the day seriously affects daily activities; cough seriously affects sleep at night. | |
Other clinical symptoms: |
Efficacy evaluation
Evaluation indexes of safety
Drug cost estimation
Statistical analysis
Results
Evaluation of efficacy after treatment (6 months)
Chest CT data
Arterial blood gas
Indexes | Before treatment VS 6 months (n = 20) | Before treatment VS 12 months (n = 17) | ||||
---|---|---|---|---|---|---|
Before treatment | 6 months | P value | Before treatment | 12 months | P value | |
Oxygen partial pressure(mmHg) | 69.05 ± 1.14 | 88.16 ± 15 | < 0.001 | 67.56 ± 11.42 | 81.25 ± 13.55 | 0.002 |
Alveolar-arterial oxygen partial pressure difference(mmHg) | 35.77 ± 16.00 | 18.1 ± 13.69 | 0.001 | 35.84 ± 15.52 | 28.75 ± 12.21 | 0.220 |
FVC(L) | 3.34 ± 0.88 | 3.54 ± 0.83 | 0.022 | 3.165 ± 0.952 | 3.365 ± 0.849 | 0.139 |
DLCO (%) | 69.65 ± 22.49 | 84.49 ± 13.73 | 0.004 | 68.75 ± 26.02 | 89.24 ± 14.70 | 0.010 |
Six-minute walking distance(miles) | 501.9 ± 133.22 | 645 ± 117.18 | 0.002 | 486.0 ± 134.0 | 624.0 ± 149.7 | 0.021 |
Pulmonary function
Symptom score
Six-minute walking test
Judgment of efficacy
Evaluation of efficacy after 12 months fellow up
(A) Changes of CT paving stone sign score before treatment and after 6 months of treatment (n = 20) | ||
Scores before treatment | Scores after 6 months of treatment | Number of cases |
2 | 1 | 4 |
2 | 2 | 2 |
3 | 1 | 4 |
3 | 2 | 4 |
3 | 3 | 1 |
4 | 1 | 1 |
4 | 2 | 1 |
5 | 0 | 1 |
5 | 1 | 2 |
(B) Changes of CT paving stone signs score before treatment and after 12 months of treatment (n = 17) | ||
Scores before treatment | Scores after 12 months of treatment | Number of cases |
2 | 1 | 3 |
2 | 2 | 1 |
3 | 1 | 5 |
3 | 2 | 1 |
3 | 3 | 2 |
4 | 3 | 1 |
4 | 1 | 1 |
5 | 1 | 2 |
5 | 2 | 1 |
(A) Changes of cough scores before treatment and after 6 months of treatment (n = 20) | ||
Scores before treatment | Scores after 6 months of treatment | Number of cases |
0 | 0 | 2 |
1 | 0 | 1 |
1 | 1 | 5 |
2 | 1 | 10 |
3 | 1 | 2 |
(B) Changes of cough scores before treatment and after 12 months of treatment (n = 17) | ||
Scores before treatment | Scores after 12 months of treatment | Number of cases |
0 | 0 | 1 |
1 | 0 | 1 |
1 | 1 | 3 |
1 | 2 | 1 |
2 | 1 | 8 |
2 | 2 | 1 |
3 | 1 | 2 |
(A): Changes of polypnea scores before treatment and after 6 months of treatment (n = 20) | ||
Scores before treatment | Scores after 6 months of treatment | Number of cases |
1 | 1 | 4 |
2 | 1 | 4 |
3 | 1 | 4 |
3 | 2 | 3 |
4 | 1 | 4 |
5 | 1 | 1 |
(B): Changes of polypnea scores before treatment and after 12 months of treatment (n = 17) | ||
Scores before treatment | Scores after 12 months of treatment | Number of cases |
1 | 0 | 1 |
1 | 1 | 2 |
2 | 0 | 1 |
2 | 1 | 1 |
2 | 3 | 1 |
3 | 0 | 2 |
3 | 1 | 3 |
3 | 2 | 1 |
3 | 3 | 1 |
4 | 1 | 3 |
5 | 1 | 1 |
Cure | Improved | Invalidity or deterioration | Effective cases (Effective rate) | |
---|---|---|---|---|
End of treatment(6 months) | 1 | 16 | 3 | 17/20(85%) |
End of follow-up (12 months) | 0 | 14 | 3 | 14/17(82.35%) |
Medication method | Minimum Dose x Minimum Time | RMB (yuan) | Maximum Dose x Maximum Time | RMB (yuan) |
---|---|---|---|---|
Inhalation | 250μg qd × 14 weeks, 4 days-on, 4 days-off | 15,190 | 500μg bid*68 weeks | 344,306 |
Subcutaneous injection | 9μg/kg/day*12 weeks | 32,811 | 18μg/kg/d*52 weeks | 284,357 |
This method | 75μg qd*6 months | 7324 | 150μg qd*6 months | 13,020 |