[重组人脱氧核糖核酸酶对黏液黏稠病儿童及青少年呼吸功能和营养状况的影响]

Wizla-Derambure N, Michaud L, Sardet A, Deschildre A, Loeuille G A, Tassin E, Loire N, Buisine C, Boutry E, Dias J, Hecquet F, Turck D

Centre de soins pour la Mucoviscidose, Clinique de Pédiatrie, Hôpital Jeanne-de-Flandre, Lille, France.

Arch Pediatr. 1998 Apr;5(4):378-83. doi: 10.1016/s0929-693x(98)80023-7.

BACKGROUND

In 1994 we started recombinant human deoxyribonuclease (rhDNase) in every cystic fibrosis (CF) patient whatever his (her) clinical condition, provided they were aged more than 5 years and forced vital capacity (FVC) was > or = 40%.

POPULATION AND METHODS

We reviewed retrospectively the effects of rhDNase in 69 CF children and adolescents during a 2-year follow-up. Patients (35 boys, 34 girls) received 2.5 mg of rhDNase once daily from a mean age of 8.5 years (range 5-16.4). Baseline spirometric values (% predicted) and nutritional status were as followed: FVC = 84.8 +/- 21.7; forced expiratory volume in 1 second (FEV1) = 80.8 +/- 22.2; peak flow = 89.7 +/- 34.2, forced expiratory fraction 25-75% (FEF 25-75) = 71.8 +/- 32.8; Z score weight/height = -0.41 +/- 1.14; Z score weight/age = -0.48 +/- 1.25, body mass index = 15.4 +/- 1.8; caloric intake = 107 +/- 25% of recommended dietary allowances (RDA). Patients had a Shwachman-Kulczycki's score of 87 +/- 9. Spirometric and nutritional data were analysed after 1, 3, 6, 12, 18 and 24 months of treatment and compared to baseline values (changes evaluated as percent change from mean baseline for spirometric data). Shwachman-Kulczycki's score was calculated after 24 months of rhDNase.

RESULTS

An improvement of FVC (+10.7%, P < 0.001) and FEV1 (+12%, P < 0.01) was noted after one month of treatment and was maintained throughout the following 2 years around 8.7% (6.4-11.4) for FVC and 8.2% (7.3-9.1) for FEV1, P < or = 0.01. This was particularly observed in children aged 5 to 10 years, in boys and in patients with a baseline FVC under 70% predicted. There was no significant change in FEF 25-75. We observed an improvement of daily caloric intake from the third month (P < 0.05) and of body mass index from the sixth month (P = 0.02). This was particularly noted in girls. Z score weight/age was improved only during the first 3 months of treatment while Z score weight/height increased only after a 2 year follow-up. There was no significant change in Shwachman-Kulczycki's score after 24 months of rhDNase.

CONCLUSION

rhDNase in CF children in effective on lung function as well as on nutritional status and the response to this treatment can be evaluated after the first 3 months.

背景

1994年，我们开始对每一位囊性纤维化（CF）患者使用重组人脱氧核糖核酸酶（rhDNase），无论其临床状况如何，条件是患者年龄超过5岁且用力肺活量（FVC）≥40%。

研究对象与方法

我们回顾性分析了69例CF儿童和青少年在2年随访期间使用rhDNase的效果。患者（35名男孩，34名女孩）从平均8.5岁（范围5 - 16.4岁）开始，每日一次接受2.5毫克rhDNase治疗。基线肺功能测定值（预测值百分比）和营养状况如下：FVC = 84.8±21.7；第1秒用力呼气量（FEV1）= 80.8±22.2；峰值流速 = 89.7±34.2；25% - 75%用力呼气分数（FEF 25 - 75）= 71.8±32.8；身高体重Z评分 = -0.41±1.14；年龄体重Z评分 = -0.48±1.25；体重指数 = 15.4±1.8；热量摄入 = 推荐膳食摄入量（RDA）的107±25%。患者的Shwachman - Kulczycki评分为87±9。在治疗1、3、6、12、18和24个月后分析肺功能和营养数据，并与基线值进行比较（肺功能数据变化以相对于平均基线的百分比变化来评估）。在使用rhDNase 24个月后计算Shwachman - Kulczycki评分。

结果

治疗1个月后，FVC（+10.7%，P < 0.001）和FEV1（+12%，P < 0.01）有所改善，并在随后的2年中保持，FVC约为8.7%（6.4 - 11.4），FEV1约为8.2%（7.3 - 9.1），P≤0.01。这在5至10岁的儿童、男孩以及基线FVC低于预测值70%的患者中尤为明显。FEF 25 - 75没有显著变化。我们观察到从第3个月起每日热量摄入有所改善（P < 0.05），从第6个月起体重指数有所改善（P = 0.02）。这在女孩中尤为明显。年龄体重Z评分仅在治疗的前3个月有所改善，而身高体重Z评分仅在2年随访后有所增加。使用rhDNase 24个月后，Shwachman - Kulczycki评分没有显著变化。