Department of Pediatrics, MetroHealth Medical Center, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Department of Neurosciences DNS, University of Padova, Padova, Italy.
Lancet Respir Med. 2022 Apr;10(4):403-420. doi: 10.1016/S2213-2600(21)00581-6.
The life-limiting complications of Duchenne muscular dystrophy (DMD) include loss of lung function and progressive cardiomyopathy; when patients are treated with assisted ventilation, cardiac function becomes the main determinant of survival. Therapy for DMD is changing rapidly, with the emergence of new genetic and molecular therapeutic options, the proliferation of which has fostered the perception that DMD is a potentially curable disease. However, data for respiratory and cardiac outcomes are scarce and available evidence is not uniformly positive. Patients who share a dystrophin (DMD) genotype can have highly divergent cardiorespiratory phenotypes; genetic modifiers of DMD gene expression are a probable cause of respiratory and cardiac phenotypic variability and discordance. In this Personal View, we provide an overview of new and emerging DMD therapies, highlighting the limitations of current research and considering strategies to incorporate cardiorespiratory assessments into clinical trials. We explore how genetic modifiers could be used to predict cardiorespiratory natural history and how manipulation of such modifiers might represent a promising therapeutic strategy. Finally, we examine the changing role of respiratory physicians, cardiologists, and intensive care clinicians on the frontline of a challenging new clinical landscape.
杜氏肌营养不良症（DMD）的生命限制并发症包括肺功能丧失和进行性心肌病；当患者接受辅助通气治疗时，心脏功能成为生存的主要决定因素。DMD 的治疗方法正在迅速变化，新的基因和分子治疗选择不断涌现，这使得人们认为 DMD 是一种潜在可治愈的疾病。然而，有关呼吸和心脏结局的数据很少，可用证据并不完全是肯定的。具有相同肌营养不良蛋白（DMD）基因型的患者可能具有高度不同的心肺表型；DMD 基因表达的遗传修饰因子可能是呼吸和心脏表型变异性和不一致性的原因。在这篇个人观点中，我们概述了新出现的 DMD 治疗方法，强调了当前研究的局限性，并考虑了将心肺评估纳入临床试验的策略。我们探讨了遗传修饰因子如何用于预测心肺自然史，以及对这些修饰因子的操纵如何代表一种有前途的治疗策略。最后，我们研究了呼吸科医生、心脏病专家和重症监护临床医生在充满挑战的新临床领域中的前沿作用的变化。
