Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, United States.
Biological Sciences Graduate Program, University of Maryland, College Park, MD 20742, United States.
Adv Drug Deliv Rev. 2023 Jul;198:114858. doi: 10.1016/j.addr.2023.114858. Epub 2023 May 12.
Asthma is a chronic lung disease affecting millions worldwide. While classically acknowledged to result from allergen-driven type 2 inflammatory responses leading to IgE and cytokine production and the influx of immune cells such as mast cells and eosinophils, the wide range in asthmatic pathobiological subtypes lead to highly variable responses to anti-inflammatory therapies. Thus, there is a need to develop patient-specific therapies capable of addressing the full spectrum of asthmatic lung disease. Moreover, delivery of targeted treatments for asthma directly to the lung may help to maximize therapeutic benefit, but challenges remain in design of effective formulations for the inhaled route. In this review, we discuss the current understanding of asthmatic disease progression as well as genetic and epigenetic disease modifiers associated with asthma severity and exacerbation of disease. We also overview the limitations of clinically available treatments for asthma and discuss pre-clinical models of asthma used to evaluate new therapies. Based on the shortcomings of existing treatments, we highlight recent advances and new approaches to treat asthma via inhalation for monoclonal antibody delivery, mucolytic therapy to target airway mucus hypersecretion and gene therapies to address underlying drivers of disease. Finally, we conclude with discussion on the prospects for an inhaled vaccine to prevent asthma.
哮喘是一种影响全球数百万人的慢性肺部疾病。虽然经典上认为它是由过敏原驱动的 2 型炎症反应引起的，导致 IgE 和细胞因子的产生以及免疫细胞如肥大细胞和嗜酸性粒细胞的涌入，但哮喘病理生物学亚型的广泛范围导致了对抗炎治疗的高度可变反应。因此，需要开发能够针对哮喘肺部疾病全谱的患者特异性治疗方法。此外，将针对哮喘的靶向治疗直接递送到肺部可能有助于最大限度地提高治疗效果，但在设计用于吸入途径的有效制剂方面仍然存在挑战。在这篇综述中，我们讨论了对哮喘疾病进展的现有理解，以及与哮喘严重程度和疾病恶化相关的遗传和表观遗传疾病修饰因子。我们还概述了哮喘临床可用治疗方法的局限性，并讨论了用于评估新疗法的哮喘临床前模型。基于现有治疗方法的缺点，我们强调了通过吸入途径治疗哮喘的最新进展和新方法，包括用于单克隆抗体递送的吸入疫苗、针对气道粘液过度分泌的粘液溶解疗法和针对疾病潜在驱动因素的基因疗法。最后，我们讨论了吸入疫苗预防哮喘的前景。
