Respiratory disease is a leading cause of morbidity in people with Duchenne muscular dystrophy and also occurs in the golden retriever muscular dystrophy (GRMD) model. We have previously shown that adult GRMD dogs have elevated expiratory flow as measured non-invasively during tidal breathing. This abnormality likely results from increased chest and diaphragmatic recoil associated with fibrosis and remodeling. Treatments must reverse pathologic effects on the diaphragm and other respiratory muscles to maximally reduce disease morbidity and mortality. Here, we extended our work in adults to younger GRMD dogs to define parameters that would be helpful in preclinical trials. Tidal breathing spirometry and respiratory inductance plethysmography were performed in GRMD dogs at approximately 3 and 6 months of age, corresponding to approximately 5-10 years in DMD, when clinical trials are often conducted. Expiratory flows were markedly elevated in GRMD versus normal dogs at 6 months. Values increased in GRMD dogs between 3 and 6 months, providing a 3-month window to assess treatment efficacy. These changes in breathing mechanics have not been previously identified at such an early age. Expiratory flow measured during tidal breathing of unsedated young GRMD dogs could be a valuable marker of respiratory mechanics during preclinical trials.

中文翻译：

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金毛肌营养不良症幼犬的呼气功能障碍


呼吸系统疾病是杜氏肌营养不良症患者发病的主要原因，也发生在金毛寻回犬肌营养不良症 (GRMD) 模型中。我们之前已经表明，成年 GRMD 狗在潮式呼吸期间无创测量时呼气流量升高。这种异常可能是由于与纤维化和重塑相关的胸部和膈肌反冲力增加所致。治疗必须逆转对膈肌和其他呼吸肌的病理影响，以最大限度地降低疾病的发病率和死亡率。在这里，我们将我们在成人身上的工作扩展到年轻的 GRMD 狗，以确定有助于临床前试验的参数。潮式呼吸肺活量测定法和呼吸感应体积描记法是在大约 3 个月和 6 个月大的 GRMD 犬中进行的，相当于 DMD 大约 5-10 岁，此时经常进行临床试验。 6 个月时，GRMD 犬的呼气流量与正常犬相比显着升高。 GRMD 犬的数值在 3 至 6 个月之间有所增加，为评估治疗效果提供了 3 个月的窗口期。以前在这么小的年纪并没有发现这些呼吸力学的变化。在未镇静的幼年 GRMD 狗的潮式呼吸过程中测量的呼气流量可能是临床前试验期间呼吸力学的有价值的标志。