Milla C E
Cystic Fibrosis Center, University of Minnesota, Minneapolis, USA.
Thorax. 1998 Dec;53(12):1014-7. doi: 10.1136/thx.53.12.1014.
After multiple studies, including clinical trials, suggested some mild clinical benefits from the use of rhDNase by patients with cystic fibrosis, a widespread acceptance of the drug has followed. However, long-term effects, specifically on lung disease progression, have not been demonstrated. Experience with the use of this drug in a single cystic fibrosis centre is presented and compared with the trends seen in the patient population of the centre before the introduction of the drug.
Patients with cystic fibrosis routinely followed at the University of Minnesota Cystic Fibrosis Center and prescribed rhDNase for at least two years were included in this retrospective study. Data on spirometric parameters (FEV1 and FEV1/FVC), allometric index, and admissions to hospital were retrieved from the centre's database for the two years preceding the prescription of rhDNase and the two years that followed. Trends in pulmonary function and allometric index were analysed by mixed linear modelling, and hospital admission rates for both periods were calculated and compared.
One hundred and ninety patients met the inclusion criteria for the study. In the two years preceding the prescription of rhDNase the trends noted were those of a mild decline in FEV1, a stable FEV1/FVC, and a mild improvement in allometric index. In the two years that followed the prescription of rhDNase a mild decline in all these parameters occurred which was a significant change from the previous period (all p < 0.009). There was no difference between females and males in the trends experienced after the start of rhDNase. By logistic regression analysis only the presence of malnutrition at the time of prescription was associated with a positive trend after the introduction of rhDNase. No significant change in the hospital admission rates occurred, with rates of 0.52 (0.16) and 0.56 (0.21) admissions/patient/year for the periods before and after the prescription of rhDNase, respectively.
The introduction of rhDNase to the regimen of patients with cystic fibrosis cared for at this centre has not been followed by a positive trend in lung function and nutritional parameters. There are some differences between this patient population and those who participated in previous studies which may help to explain the contrasting findings of this study. However, it is also possible that factors other than mucus clearance need to be improved to achieve a favourable response in disease progression. Patients on this treatment should be followed closely and the benefit judged on an individual basis. More studies are needed to define better the specific indications and use of this form of treatment.
经过包括临床试验在内的多项研究表明，囊性纤维化患者使用重组人脱氧核糖核酸酶（rhDNase）有一些轻微的临床益处，之后该药物得到了广泛认可。然而，其长期影响，特别是对肺部疾病进展的影响尚未得到证实。本文介绍了在一个单一的囊性纤维化中心使用该药物的经验，并与该中心在引入该药物之前患者群体的趋势进行了比较。
本回顾性研究纳入了明尼苏达大学囊性纤维化中心常规随访且处方rhDNase至少两年的囊性纤维化患者。从该中心数据库中检索rhDNase处方前两年和处方后两年的肺功能参数（第一秒用力呼气容积[FEV1]和FEV1/用力肺活量[FVC]）、体质量指数以及住院情况的数据。通过混合线性模型分析肺功能和体质量指数的趋势，并计算和比较两个时期的住院率。
190名患者符合研究纳入标准。在rhDNase处方前两年，观察到的趋势是FEV1轻度下降、FEV1/FVC稳定以及体质量指数轻度改善。在rhDNase处方后的两年里，所有这些参数都出现了轻度下降，与前一时期相比有显著变化（所有p<0.009）。rhDNase开始使用后，女性和男性经历的趋势没有差异。通过逻辑回归分析，只有处方时存在营养不良与引入rhDNase后的积极趋势相关。住院率没有显著变化，rhDNase处方前和处方后时期的住院率分别为0.52（0.16）次/患者/年和0.56（0.21）次/患者/年。
在该中心接受治疗的囊性纤维化患者的治疗方案中引入rhDNase后，肺功能和营养参数并未呈现积极趋势。该患者群体与之前参与研究的患者群体存在一些差异，这可能有助于解释本研究的对比结果。然而，也有可能除了黏液清除之外，还需要改善其他因素才能在疾病进展中获得良好反应。接受这种治疗的患者应密切随访，并根据个体情况判断获益情况。需要更多研究来更好地确定这种治疗形式的具体适应证和用法。
