Supplementary Material for: The Efficacy and Safety of Stepwise Oral Food Challenge in Children with Cow’s Milk Allergy

<b><i>Introduction:</i></b> Stepwise oral food challenge (OFC) tests begin with low doses of allergens and progress to full doses. We previously reported the safety and efficacy of stepwise OFC for reintroducing hen eggs. In this study, we discuss its application for cow’s milk (CM) allergy. <b><i>Methods:</i></b> We included 927 children (median age, 3.2 years) who underwent CM-OFC between 2017 and 2021. The target challenge dose was classified as low (&lt;10 mL), middle (≥10 mL but &lt;100 mL), or full. When participants reacted to the low dose, they underwent a very low-dose OFC using baked milk or &lt;1 mL of CM. <b><i>Results:</i></b> Positive reactions occurred in 210 cases (22.7%), including 69 anaphylactic reactions (7.4%). A lower target dose resulted in more positive OFC results (<i>p</i> &lt; 0.001) and anaphylaxis (<i>p</i> = 0.001). The lower dose group included more children with complete elimination of CM (<i>p</i> &lt; 0.001), with numerous histories of anaphylaxis induced by CM (<i>p</i> &lt; 0.001), and higher levels of total IgE (<i>p</i> = 0.033) and CM-sIgE (<i>p</i> &lt; 0.001). A multivariate analysis indicated that in the low-dose-OFC group, higher CM-sIgE levels (<i>p</i> = 0.034), younger age (<i>p</i> = 0.005), and complete elimination of CM (<i>p</i> = 0.002) were associated with positive OFC results. <b><i>Conclusion:</i></b> The stepwise OFC could reintroduce small amounts of CM, even in cases with high CM-sIgE levels or a history of anaphylaxis. Performing CM-OFC at younger ages, specifically from infancy, with very low doses, might facilitate the safe reintroduction of CM.引言：逐步口服食物激发试验（Oral Food Challenge, OFC）以低剂量过敏原为起始剂量，逐步递增至全剂量。本团队此前已报道了逐步口服食物激发试验用于鸡蛋重新引入的安全性与有效性，本研究旨在探讨该试验在牛乳（Cow’s Milk, CM）过敏中的应用价值。 方法：本研究纳入2017至2021年间接受牛乳口服食物激发试验（CM-OFC）的927名儿童，受试者年龄中位数为3.2岁。将目标激发剂量划分为低剂量组（＜10 mL）、中剂量组（≥10 mL且＜100 mL）与全剂量组。若受试者对低剂量产生反应，则采用焙烤牛乳或＜1 mL的牛乳为其实施极低剂量口服食物激发试验。 结果：共计210例受试者出现激发试验阳性反应（占比22.7%），其中69例为过敏性反应（占比7.4%）。目标激发剂量越低，口服食物激发试验阳性结果发生率越高（p < 0.001），过敏性反应发生率亦越高（p = 0.001）。低剂量组中，完全回避牛乳饮食的儿童占比更高（p < 0.001），有牛乳诱发过敏性反应病史的儿童占比更高（p < 0.001），且总IgE水平（p = 0.033）与牛乳特异性IgE（CM-sIgE）水平（p < 0.001）亦更高。多因素分析结果显示，在低剂量口服食物激发试验组中，更高的牛乳特异性IgE水平（p = 0.034）、更年幼的年龄（p = 0.005）以及完全回避牛乳饮食（p = 0.002）均与口服食物激发试验阳性结果显著相关。 结论：逐步口服食物激发试验可帮助牛乳过敏受试者安全重新摄入少量牛乳，即便对于牛乳特异性IgE水平较高或有过敏性反应病史的受试者亦适用。在年幼阶段（尤其婴儿期）采用极低剂量开展牛乳口服食物激发试验，或可助力牛乳的安全重新摄入。