SILDENAFIL EFFECTS ON EXERCISE AND PULMONARY FUNCTION IN CYSTIC FIBROSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。囊性纤维化（CF）肺疾病的特征在于持续的气道炎症和实质破坏。这导致肺功能的进行性下降和慢性间歇性缺氧。由于缺氧和炎症引起的进行性肺血管疾病（PVD）增加了肺血管阻力，并可能导致明显的右心室衰竭。在心脏受累之前，PVD的早期临床表现包括运动耐量受限和呼吸困难。PVD导致CF患者运动耐量和生活质量下降的程度尚不清楚。通过标准化运动测试和超声心动图评估，可以在CF患者中识别出PVD的早期证据。在右心室受累发作之前识别出患有PVD的CF患者可能允许药物干预以减缓这种疾病的进展。最近的研究表明，磷酸二酯酶5型抑制剂西地那非的管理可以显着降低肺血管阻力，提高非CF患者的运动耐量。西地那非可能被证明是治疗CF患者肺血管疾病的有效口服药物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and parenchymal destruction. This leads to a progressive decline in pulmonary function and periods of chronic intermittent hypoxia. Progressive pulmonary vascular disease (PVD) due to hypoxia and inflammation increases pulmonary vascular resistance and may lead to overt right ventricular failure. Early clinical manifestations of PVD prior to the development of cardiac involvement include limitations in exercise tolerance and dyspnea. The extent to which PVD contributes to the decline in exercise tolerance and quality of life in CF patients is not known. Early evidence of PVD may be recognized in CF patients through standardized exercise testing and echocardiographic evaluation. Identifying those CF patients with PVD prior to the onset of right ventricular involvement may allow pharmacologic intervention to attenuate the progression of this disease. Recent studies have demonstrated the administration of the phosphodiesterase type 5-inhibitor sildenafil can markedly decrease pulmonary vascular resistance and improve exercise tolerance in non-CF patients. Sildenafil may prove to be an efficacious oral pharmacologic agent for the treatment of pulmonary vascular disease in patients with CF.