Although growth velocity returns to normal within a few years after the initiation of inhaled glucocorticoid therapy (resulting in a deficit in height that is not progressive), the long-term effect of the initial decrease in growth velocity on attainment of adult height is still unclear. Retrospective, cross-sectional studies of the effect of inhaled glucocorticoid therapy in child- hood on the attainment of adult height have had conflicting results. In one small longitudinal study, there was no significant difference between actual adult height and predicted adult height in 142 participants who had received budesonide in variable daily doses (mean, 427 μg) during childhood for a mean of 9.2 years.
成人身長と9.2年の平均のための幼年期の間に（427μgの平均値）変数日用量でブデソニドを受けていた142の参加者における予測成人身長との間に有意差は認められなかった。
At the end of the CAMP clinical trial, we predicted that the children receiving budesonide for a mean follow-up of 4.3 years would attain the same adult height as the children receiving nedocromil or placebo. It has been hypothesized that children receiving inhaled glucocorticoids grow for a longer period of time, eventually catching up and having no long-term effects from the decreased growth velocity seen in the first few years of therapy. Thus, the effect of inhaled glucocorticoids on height has often been characterized as growth retardation rather than growth suppression.
We later reported that the heights of the participants in the budesonide group had not caught up with the heights of participants in the placebo group after an additional 4.8 years of follow-up (total, 9.1 years), until the ages of 12 to 23 years.
The purpose of the current study was to continue the height follow-up of the CAMP participants to assess the effects of budesonide and nedocromil on adult height. From December 1993 through September 1995, we randomly assigned 1041 children between the ages of 5 and 13 years with mild-to-moderate asthma to one of three study groups in the double-blind, placebo-controlled CAMP trial.
最近の研究の目的は、CAMPの臨床試験の参加者の身長を追跡調査し、ブデソニドとネドクロミルが成人の身長にどのような影響を与えるか評価することにありました。1993年の12月から1995年の9月の間、CAMPの二重盲検臨床で5歳から13歳で軽~中等度喘息の1041人の子供を3つの研究グループに分け、無作為に選んだ１つのグループにプラセボを割り当てました。
今回の研究の目的は、ブデソナイドとネドクロミルが成人の身長に与える効果を測るために、CAMP参加者の身長変化のフォローアップを続けることにある。１９９３年１２月から１９９５年の９月にかけて、我々は、軽症から中程度の喘息症状がある５歳から１３歳の１０４１人の子どもたちをランダムに３つの実験グループに割り振った。それは二重盲検査法で偽薬コントロールされたCAMPの臨床である。
現在の研究の目的は、成人の高さにブデソニドおよびネドクロミルの効果を評価するCAMP参加者の高さのフォローアップを継続することでした。1993年12月から1995年9月を通して、私たちはプラセボ対象CAMP試験での、無作為二重盲検で、３つの研究グループの１つに軽度から中等度の喘息と5と13歳の1041年の子供を割り当てました。
In this study, we compared the efficacy and safety of 200 μg of budesonide administered by means of a dry-powder inhaler twice daily (400 μg per day), 8 mg of nedocromil administered by means of a metered-dose inhaler twice daily (16 mg per day), and placebo.
Albuterol was used for asthma symptoms in all three groups. The design, methods, and results of the trial have been described previously. At the end of the trial (mean follow- up, 4.3 years), the children were recruited into an observational cohort, as described previously. During follow-up, the children were treated for asthma by their primary care physicians under advisement from the CAMP physicians on the basis of the guidelines.
アルブテロールが喘息の兆候が合った場合には、アルブテロールが、この３グループで用いられた。実験デザイン、方法や結果は、前述のとおりである。臨床実験の最後（平均して４．３年のフォローアップ）で、子どもたちは前述の観察コホートに集められた。フォローアップの間、子どもたちは、CAMPのガ定めるガイドラインにより、CAMPの内科医からのアドバイスに基づいて、主治医による喘息の治療を受けていた。
アルブテロールは、3つのグループすべてに喘息症状のために使用した。試験の設計、方法および結果が、以前に記載されている。体験の終了時（平均フォローアップ、4.3年）、子どもたちは、以前に説明したように、観察コホートに採用された。追跡期間中に、子どもたちはガイドラインに基づいてCAMPの医師からの助言の下で以前の医師より喘息の治療を受けた。
Height and weight were measured every 6 months during the initial 4.5 years of observational follow-up and 1 to 2 times a year during the next 8 years. Adult height was determined at a mean age of 24.9±2.7 years. Tanner staging was performed annually until the participants were 18 years of age or attained sexual maturity. All study phases were approved by the institutional review board at each study center.
Participants who were 18 years of age or older provided written informed consent; those under the age of 18 years provided assent, with written informed consent provided by their parents or guardians.
18歳以上の参加者は、臨床方針に納得したことを示すインフォームド・コンセントの同意書を文章で提出し、18歳未満の参加者は同意書と親か保護者のインフォームド・コンセントを文章で提出することになっています。
１８歳以上の被験者からは、書面によるインフォームド・コンセントが提出され、１８歳未満の被験者については、親や保護者の手による書面のインフォームド・コンセントとともに、同意がなされていた。
At each clinic visit, a trained technician used a stadiometerto measure height, as described in the protocol, and investigators obtained an interim history of participants’ health and medication use.During the first 8 years of follow-up, this information was supplemented with information obtained during telephone contacts that were evenly spaced around the clinic visits. On the basis of reported recommendations, adult height was defined as either the mean of all measurements performed at the age of 18 years or older for women and at the age of 20 years or older for men.
if height was not measured at these ages, the most recently obtained height that was less than 1 cm greater than a height obtained at least 1 year previously.
We used a multiple linear regression model to compare mean height in the budesonide and nedocromil groups with that in the placebo group, with adjustment for eight covariates at trial entry: age, race or ethnic group, sex, clinic, height, duration of asthma (<3 years, ≥3 to <7 years, or ≥7 years), severity of asthma (moderate or mild), and presence or absence of skin-test reactivity. Data for each participant were analyzed in the study group to which the participant had been randomly assigned, regardless of subsequent asthma treatment.
私たちは、プラセボ群とブデソニドとドクロのグループの平均の高さを比較するために、年齢、人種や民族、性別、診療所、身長、喘息の期間（<3年、≥3<7年、もしくは≥7年）、喘息の深刻度合（中程度または軽度）、皮膚テスト反応性のあるなし、などといった変量の調整しながら、重回帰モデルを使用しました。各参加者のデータは、その後の喘息治療に関わらず、参加者から無作為に選別された研究グループで分析された。
一番新しく測られた身長は少なくとも1年以上前に測定された身長より1cm弱ほど高い。
私どもは、偽薬グループの平均身長とブデソニドとネドクロミルグループの平均身長を比べるため、複数の線形回帰モデルを使った。
参加者を８つの共変数で調整：年齢、人種や民族、性別、病院、身長、喘息の長さ（３年以内、３年以上７年以下、７年以上）
喘息の重さ（普通、軽め）、肌テストの反応あり、なし。
続いて起こる喘息治療に関わらず、研究グループにおいてそれぞれの適当に割り当てられた参加者たちのデータが分析された。
The adjusted mean height in each study group was computed from the regression model at the mean values for the covariates. To assess the statistical significance of potential variations in height differences between the budesonide or nedocromil group and the placebo group across subgroups defined by race or ethnic group, age at trial entry, and duration of asthma at entry, we added covariate interaction terms to the regression model. Although these post hoc interaction tests may have a low statistical power for detecting variations in height effects across subgroups, we wanted to examine the qualitative consistency of the budesonide and nedocromil effects across subgroups.
偽薬グループとブデソニド、ネドクロミルグループおよび、人種、民族ならびに、年齢で規定された区分別グループ、喘息をわずらっている期間で規定された区分別グループで統計的に重要な身長の変化の可能性を査定するため、私どもは回帰モデルに共変数相互作用項をくわえた。相互テストの論理的な誤りが統計的にグループの身長の変化を見出す作用を低めるとしても、全ての区分別グループにおけるブデソニドとネドクロミルの効果の定性的一貫性を研究したかった。
We used chisquare tests for categorical variables and t-tests for continuous variables to assess differences in baseline characteristics between participants for whom data regarding adult height were missing and those for whom such data were available. We used logistic-regression analysis to check for systematic differences between participants with adult-height data and those without such data with respect to study- group distribution in subgroups, as defined by the baseline covariates. Effects of missing data on adult height were further addressed in sensitivity analyses with the use of two alternative methods to impute missing adult height.
In the first method, we used a single imputation of adult height on the basis of bone age obtained at the end of the trial and the equations of Tanner et al.In the second method, we used multivariate multiple imputation with 13 imputations from simulations of a Bayesian posterior predictive distribution of the missing data, using an iterative Markov chain Monte Carlo method based on the multivariate normal distribution provided by Stata software. All eight covariates in the model for difference in adult height were used together with serial height measurements obtained 2 to 102 months after trial entry. The missing adult height data were assumed to be missing completely at random.
文章間にスペースが入りましたが、詰めてください。よろしくお願いします。