Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable “alternative” option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not “class‐related,” as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities.

中文翻译：

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舌下免疫治疗 30 年

过敏原免疫疗法 (AIT) 在 100 多年前以经验为基础被引入临床实践。自第一次尝试以来，AIT 是皮下给药的。事实上，其他给药途径被提出和研究，特别是为了提高安全性，但只有舌下途径（SLIT）基于证据获得了可信度，然后被接受为皮下途径的可行“替代”选择。在过去的 30 年中，SLIT 主要用于临床试验和临床实践。因此，大量数据来自对照试验和上市后监测研究。很明显，SLIT 总体上是有效的，但同样清楚的是，疗效与荟萃分析得出的“类别相关”无关，而是仅限于每个特定产品。SLIT 30 年的持续使用使许多临床方面得到澄清，例如疗效、安全性、在哮喘中的使用、给药方案和最佳剂量。同时阐明了AIT的作用机制，并提出了新的适应症（如食物过敏、特应性皮炎）。此外，引入基于分子的诊断，可以根据特定的致敏情况更好地细化 SLIT 的处方。本文将描述 SLIT 治疗呼吸道过敏的起源和演变，考虑到建议这种治疗形式的临床背景、最近发展的方面、未来前景和未满足的需求，因此，这不是系统评价，而是对过去历史的叙述性历史描述，以及对未来机遇的展望。