每日1次吸入式皮质类固醇可轻微抑制儿童生长

Cochrane系统评价数据库7月16日在线发表的一篇Cochrane评价指出，每日1次使用低至中等剂量吸入式皮质类固醇治疗轻至中度持续性哮喘可轻微抑制所有年龄儿童的生长。

这一水平的使用与第1年治疗期间线性生长速率平均降低0.48 cm/年相关，而背景平均生长速率为6~9 cm/年。这一生长抑制效应在后续几年的治疗中不那么明显，并且生长抑制程度与所用的特定药物的关联强于与剂量或给药装置的关联（Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]）。

这项综合评价由巴西里奥格兰德联邦大学的Linjie Zhang医生及其同事进行，共入选25项质量良好的平行组、随机临床试验，涉及8471例最大年龄为18岁的儿童，其中5128例接受吸入式皮质类固醇治疗，3343例接受非甾体抗炎药或安慰剂治疗并作为对照者。大部分试验设盲，并且多数为多中心试验。25项试验中有17项为药企资助。

参与试验的儿童使用通过任何类型的吸入装置给药的倍氯米松、布地奈德、环索奈德、氟尼缩松，氟替卡松或莫米松，并被随访3个月至6年。

结果显示，所有6种吸入式皮质类固醇均在1年治疗期间抑制线性生长速率（主要终点），并且也均抑制次要终点测定的生长。次要终点为身高标准偏差评分随时间推移的变化和身高随时间推移相对基线的变化。这些效应在后续几年的治疗中不那么明显，但持续至患者达到其成年身高。

一项从青春期前随访至成人期的试验发现，与未使用吸入式皮质类固醇的患者相比，使用吸入式皮质类固醇的患者的成年身高平均降低1.2 cm。

研究者指出，日剂量、给药装置和患者年龄对生长抑制程度无显著影响。少数比较各种皮质类固醇的研究显示，倍氯米松和布地奈德抑制生长的作用稍强于其他4种药物。然而，荟萃分析不是探讨这些问题的最佳方法，并且需进行更多的头对头随机试验以证实这些结果。

这些结果表明，吸入式皮质类固醇应在最低有效剂量水平使用。此外，鉴于这些药物的个体易感性存在较大差异，对接受吸入式皮质类固醇治疗的儿童进行线性生长方面的监测是比较稳妥的做法。

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By: MARY ANN MOON, Internal Medicine News Digital Network

Daily use of low- to medium-dose inhaled corticosteroids for mild to moderate persistent asthma suppresses growth to a "small" degree in children of all ages, according to a Cochrane review published online July 16 in the Cochrane Database of Systematic Reviews.

This level of use was associated with a mean reduction of 0.48 cm per year in linear growth velocity during the first year of treatment, against a background average growth rate of 6-9 cm per year. The growth suppression was less pronounced in subsequent years of treatment, and the magnitude of growth suppression was more strongly related to the particular drug used than to the dose or delivery device, said Dr. Linjie Zhang of the Federal University of Rio Grande (Brazil) and his associates.

Daily use of low- to medium-dose inhaled corticosteroids suppresses growth to a "small" degree in children, according to the review.

aa"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimeter less during the first year of treatment. But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared with the known benefits of the drugs for controlling asthma and ensuring full lung growth," Dr. Zhang said in a press statement accompanying the report.

The investigators undertook this comprehensive review of the literature and metaanalysis because of persistent concerns about possible adverse effects of inhaled corticosteroids on children’s growth and because several recent randomized trials have examined the issue and have assessed newly available agents and modes of delivery. They identified 25 good-quality, parallel-group, randomized clinical trials involving 8,471 children up to age 18, of whom 5,128 were treated with inhaled corticosteroids and 3,343 were treated with nonsteroidal anti-inflammatory drugs or placebo and served as controls.

Most of the trials were blinded, and most were multicenter. Seventeen of the 25 were funded by pharmaceutical companies.

The participating children used beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, or mometasone, delivered by any type of inhalation device, and were followed for 3 months to 6 years.

All six inhaled corticosteroids were found to suppress linear growth velocity during 1 year of treatment, which was the primary outcome of interest. They all also suppressed growth as measured by the secondary outcomes of change in height standard deviation score over time and change from baseline in height over time. These effects were less pronounced in subsequent years of treatment, but persisted until patients reached their adult height.

The one study that followed prepubescent participants into adulthood showed that those who used inhaled corticosteroids had a mean reduction of 1.2 cm in adult height, compared with those who did not.

Daily dose, delivery device, and patient age had had no significant impact on the magnitude of growth suppression. A small number of studies that compared the various corticosteroids against each other showed that beclomethasone and budesonide were somewhat more potent growth suppressors, compared with the other four agents. However, a meta-analysis is not the best method for exploring these issues, and data from more head-to-head randomized trials are required to confirm these findings, Dr. Zhang and his associates noted (Cochrane Database Systematic Rev. 2014 July 16 [doi:10.1002/I4651858.CD009471.pub2]).

Their findings indicate that inhaled corticosteroids should be prescribed at the lowest effective dose. "Moreover, it is prudent to monitor linear growth in children treated with inhaled corticosteroids, given that individual susceptibility to these drugs may vary considerably," the investigators added.