We obtained measurements of adult height for 943 of the original 1041 CAMP participants . Of these measurements, 96.8% were obtained from women who were at least 18 years of age or men who were at least 20 years of age; 3.2% of measurements were the most recently obtained heights that were less than 1 cm greater than a height obtained at least 1 year previously (Fig. 1). Adult height was not known for 98 participants : 35 female participants with a median age of 12 years (range, 8 to 17) and 63 male participants with a median age of 14 years (range, 7 to 19) at the last height measurement.The adjusted mean adult height was 1.2 cm lower in the budesonide group than in the placebo group (171.1 cm vs. 172.3 cm)
the mean adult height in the nedocromil group(172.1cm) was similar to that in the placebo group (Table 1 and Fig. 2). The deficit in adult height in the budesonide group, as compared with the placebo group, was greater for women (−1.8 cm) than for men (−0.8), but the effect of budesonide on adult height did not vary significantly according to sex(Table 1). Although the deficit was greater for participants who were younger at trial entry than for those who were older and greater for whites than for those of other races or ethnic groups, the effect of budesonide on adult height did not vary significantly according to the age at trial entry, race or ethnic group, or duration of asthma at trial entry.
試験開始時の年齢が若い被験者の方が、高齢の被験者よりも（プラセボ群との）身長差が大きくなり、また白人の方が他の人種や民族の投与群よりも身長差が大きくなったが、、成人身長に対するブデソニドの影響に、開始時の年齢、人種や民族、試験開始時の喘息の（持続）期間による顕著な差は認められなかった。
ブデソニド・グループの成人身長不足は、プラセボ・グループと比較して、男性（－0.8）より女性（－1.8cm）の方が大きかった。しかし、成人身長のブデソニドの効果は男女間でそれほど変化しなかった（表1）。
身長不足は、治験登録に若い参加者の方が大きかった。また白人以外の人種や民族に比較すると白人は大きかったが、成人身長に及ぼすブデソニドの効果は、治験登録時における年齢、人種または民族、喘息の持続期間で年齢によっては大きな差異は見られなかった。
The deficit in the adjusted mean height in the budesonide group, as compared with the placebo group, was 1.3 cm (−1.7 to −0.9) after 2 years of treatment and 1.2 cm (−2.0 to −0.4) at the end of the CAMP trial and persisted into adulthood without progressing further ( −1.9 to −0.5) (Fig. 2B).
Growth Velocity
Overall, age trends with respect to growth velocity in the budesonide and placebo groups differed during the first 2 years of the trial for women and men. For both sexes, the difference in velocity reduction that was seen in the first 2 years of assigned treatment in the budesonide group, as compared with the placebo group, was primarily among prepubertal participants.
発育速度
総合的にみて、ブデソナイドとプラセボグループにおける発育速度に関する年齢傾向は男女に実施されたトライアルのうち最初の2年間で分かれました。両方の性別にとって、速度の減少に現れた違いは、プラセボグループと比較してブデソナイドグループにおける最初の2年間に与えられた治療に見られたもので、その参加者は第一に思春期前の被験者とされていました。
成長速度
全体として、年齢は、女性と男性の裁判の最初の2年の間に異なったブデソニドとプラセボのグループの成長速度に関連する傾向を示している。
男女両方にとって、ブデソニド・グループで処置を受けた最初の2年で見られた速度減少の違いはプラセボ群と比較して、主に思春期前の参加者の間に見られた。
In sensitivity analyses performed to assess the potential effect of missing adult heights, the reduction in adult height in the budesonide group as compared with the placebo group was also calculated with imputation of missing adult heights based on bone age at the end of the trial and multivariate multiple imputation.
The between-group difference in adjusted mean adult height remained numerically similar to that in the primary analysis and significant for all seven alternative definitions of adult height (Table 2). At trial entry, data for participants for whom measurements of adult height were not available were similar to data for those with available measurements, except for the variable of the clinic site.
調整後の期待値で表された成人身長におけるグループ間の違いは数値的には当初の分析においては類似したままで、成人身長に関する7つの異なる定義全てにおいて優位であった（表2）。トライアル申し込み時、成人身長の計測が行われなかった参加者のデータは、計測が行われた被験者と比べて類似していた。しかし診療所の場所の変数はここには含まれない。
There was no interaction between the study group and any of the baseline covariates, suggesting that the study-group comparison among the 943 participants with known adult height may reasonably be generalized to the entire CAMP population.
Effects of Glucocorticoid Dose
During the trial period of 4 to 6 years, the mean adjusted total doses of inhaled glucocorticoids were 636.1 mg in the budesonide group and 88.5 mg in the nedocromil group versus 109.4 mg in the placebo group (P<0.001 and P = 0.14, respectively). During follow-up after the trial ended, the mean adjusted total doses were 381.0 mg in the budesonide group and 347.9 mg in the nedocromil group versus 355.0 mg in the placebo group.
糖質コルチコイド投与の効果
実験期間４－６年の間に期待値が修正された吸入糖質コルチコイドの服用量は、プラセボグループの109.4mgに対して、ブデソナイドグループで636.1ｍｇ、ネドクロミルグループが88.5mgであった (P<0.001 and P = 0.14, respectively)。実験期間終了後のフォローアップでは、期待値が修正された全体の服用量はプラセボグループの355.0mgに対して、ブデソナイドグループで381.0ｍｇ、ネドクロミルグループが347.9mgであった。
グルココルチコイド服用の影響
4～6年の治験期間に、吸入されたグルココルチコイドの平均補正合計量は、ブデソニド・グループで636.1mg、ネドクロミル・グループで88.5mgであり、プラセボ群では109.4mgでした（それぞれP < 0.001とP = 0.14）。
治験後のフォローアップの間、平均補正合計量は、ブデソニド・グループで381.0mg、ネドクロミル・グループで347.9mg、プラセボ群で355.0mgでした。
グルココルチコイド投与の効果
４年から６年にわたる実験期間に、吸入により投与されたグロココチロイドの総量の平均値は、ブデソナイドグループで、６３６．１ミリグラムであり、ネドコロミルグループで８８．５ミリグラムだったのに対し、偽薬グループでは、１０９．４ミリグラムだった。（前者は、p<0.001、後者はp=0.1４） 実験終了後のフォローアップの間に、総量の平均値は,ブデソナイドグループで381.0ミリグラム、ネドコロミルグループで347.9にたいし、偽薬グループでは、355.0ミリグラムだった。
The as-treated secondary analysis of the daily weight-adjusted dose of inhaled steroid during the first 2 years of the CAMP trial showed that a larger daily dose was associated with a lower adult height (−0.1 cm for each μg/kg). In addition, lower adult height was associated with Hispanic ethnic group and female sex, as well as a higher Tanner stage, lower height.
In an intention-to-treat analysis of the growth- suppressive effect of long-term inhaled glucocorticoid therapy for asthma initiated in children between the ages of 5 and 13 years, we found that the height deficit observed at 1 to 2 years after treatment initiation persisted into adulthood, although the deficit was neither progressive nor cumulative.
5才から13才の間の子供に始めたぜんそくの吸入式グルココルチコイドによる長期的な治療の成長抑制効果についての治療企図解析では、治療の開始から1、2年観察された身長の欠陥が大人になるまで続く。しかしその欠陥は、進行性でも増大するものでもない。
5と13歳の間の子供たちで始まる喘息の長期の吸入グルココルチコイド治療の成長／抑制効果の治療意図に基づく解析において、身長不足は進行も累積していくことはないが、処置開始後１~2年で見られた身長の伸びの遅れは成人まで持ち越すことが分かった。
5と13歳の間の子供で開始された喘息の長期吸入グルココルチコイド療法の増殖抑制効果のITTの解析においては、高さの欠陥は、プログレッシブでも累積的でもなかったが、治療開始後1〜2年で観測され、大人になっても持続することが見つかった。
Our conclusion is based on a randomized comparison of adult height, with height data available for 91% of the CAMP cohort, with the use of recognized definitions of adult height, and with consistent findings in sensitivity analyses using imputation strategies for missing data and alternative definitions of adult height (Table 2). We found little evidence that the 98 participants for whom data regarding adult height were missing differed at trial entry from the 943 participants with available data.
In contrast, the only other prospective longitudinal cohort study that followed patients into adulthood was an open-label study, and by the time the patients reached adulthood, only 15 of the original controls were available, so the investigators recruited 51 healthy siblings of the patients with asthma to be controls.The investigators in that study based their conclusion of a lack of long-term effect on height on the finding that both controls and participants receiving budesonide attained predicted adult height rather than on a randomized comparison of the adult heights reached by the two groups.
The growth-velocity deficit that we observed in the budesonide group, as compared with the placebo group, during the first 2 years of treatment was primarily among prepubertal children. Our ability to further disentangle the effects of duration of treatment, age at treatment, and puberty status during treatment on growth velocity was limited because of confounding. Nevertheless, the effect on adult height of budesonide as compared with placebo was clearly demonstrated in the CAMP population. Two previous 1-year studies of beclomethasone dipropionate also showed a greater reduction in growth in prepubertal children than in pubertal children.
Like other studies in which prepubertal children received different doses of the same inhaled glucocorticoids that have shown a dose–response effect on growth, our study showed a weight-based, dose-dependent effect in the CAMP participants. We found that a longer time since asthma diagnosis at trial entry and atopy (any positive skin test) were independent risk factors for shorter adult height. Other investigators have reported an increased incidence of short stature in children with atopy and asthma. One of these studies showed that short stature was associated with an early onset of asthma (before the age of 3 years), a finding that is consistent with our data.
訂正 （各μg/ kgにつき-0.1センチ）