Ghirardo Sergio, Mazzolai Michele, Di Marco Antonio, Petreschi Francesca, Ullmann Nicola, Ciofi Degli Atti Marta Lucia, Cutrera Renato
Pediatric Pulmonology & Respiratory Intermediate Care Unit, Academic Department of Pediatrics, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Clinical, Management and Technology Innovation Research Unit, Medical Direction, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Front Pediatr. 2022 Feb 15;10:837667. doi: 10.3389/fped.2022.837667. eCollection 2022.
We present a description of pediatric pneumology biological medications and other target therapies. The article aims at introducing the importance of a molecular approach to improve treatments. The first item treated was T2-High asthma and its current biological treatment and prescribing indications to propose a flow-chart to guide the clinical choice. Molecular rationales of such treatments are used to introduce a more general description of the biological and molecular approach to target therapies application. We introduce a general interpretation approach to neutrophilic asthma using the molecular plausibility one in order to propose possible future treatments mainly targeting interleukin-1 (IL-1), IL-17, IL-12, and IL-23. Indeed, cytokines can be excellent targets for several biological treatments. Downregulation of specific cytokines can be crucial in treating autoinflammatory and rheumatological diseases with a pulmonary involvement. Such conditions, although rare, should be early recognized as they can involve significant improvement with a properly targeted therapy. We face these conditions in a cherry-picking fashion picturing SAVI (STING-associated vasculopathy with onset in infancy), CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), and COPA (coat proteins alpha syndrome) syndrome pulmonary involvement. Such examples are functional to introduce molecular-based approach for patients with rare conditions. Molecular plausibility can be highly valuable in treating patients with not-approved but possibly highly effective therapies. Due to the rarity of these conditions, we stress the concept of basket trials using the example of cytokinin-directed immunosuppressive treatment. Lastly, we provide an example of augmentative therapy using the alpha1 antitrypsin deficiency as a model. In summary, the article presents a collection of the most recent achievements and some possible future developments of target therapies for pediatric pulmonary conditions.
我们介绍了儿科肺病的生物药物及其他靶向治疗方法。本文旨在阐述分子方法在改善治疗方面的重要性。首先讨论的是T2高哮喘及其当前的生物治疗方法和处方指征,并提出一个流程图以指导临床选择。这些治疗方法的分子原理被用于更全面地描述生物和分子方法在靶向治疗中的应用。我们运用分子合理性的一般解释方法来介绍嗜中性粒细胞性哮喘,以便提出未来可能主要针对白细胞介素-1(IL-1)、IL-17、IL-12和IL-23的治疗方法。事实上,细胞因子可以成为多种生物治疗的理想靶点。下调特定细胞因子对于治疗伴有肺部受累的自身炎症性和风湿性疾病可能至关重要。这些病症虽然罕见,但应尽早识别,因为针对性的治疗可能会带来显著改善。我们以挑选典型案例的方式探讨这些病症,如婴儿期起病的STING相关血管病(SAVI)、伴有脂肪营养不良和体温升高的慢性非典型嗜中性皮肤病(CANDLE)以及COPα综合征(coat proteins alpha syndrome)的肺部受累情况。这些例子有助于为罕见病患者引入基于分子的治疗方法。分子合理性在治疗未获批但可能非常有效的疗法的患者时可能具有很高的价值。由于这些病症的罕见性,我们以细胞因子导向的免疫抑制治疗为例强调了篮子试验的概念。最后,我们以α1抗胰蛋白酶缺乏症为例提供了增强治疗的一个示例。总之,本文介绍了儿科肺部疾病靶向治疗的最新成果以及一些未来可能的发展方向。