Clinical and Molecular Profiles of Smokers with Subclinical Interstitial Lung Disease

患有亚临床间质性肺病的吸烟者的临床和分子特征

• 批准号: 8997188
• 负责人: Ivan O. Rosas
• 金额: $ 46.19万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-17 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8997188
• 关键词: Address; Affect; Age-Years; Applications Grants; Autoimmune Process; Biological Markers; Blood; CCL18 gene; Characteristics; Chronic; Climacteric; Clinical; Clinical Trials; Clinical/Radiologic; Cross-Sectional Studies; Development; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early treatment; Enrollment; Environmental Risk Factor; Epidemiologic Studies; Family; Fibrosis; Hamman-Rich syndrome; Human; Incidence; Interstitial Lung Diseases; Intervention; Life; Longevity; Longitudinal Studies; Lung; Lung diseases; MicroRNAs; Molecular; Molecular Profiling; National Heart, Lung, and Blood Institute; Natural History; Onset of illness; Outcome; Patients; Phenotype; Physiological; Population; Populations at Risk; Prevalence; Primary Prevention; Proteins; Pulmonary Fibrosis; Quality of life; Research; Respiratory physiology; Risk; Risk Factors; Secondary Prevention; Smoker; Smoking History; Staging; Testing; Time; United States; Visual; X-Ray Computed Tomography; abstracting; cigarette smoking; clinically significant; cohort; follow-up; improved; interstitial; modifiable risk; molecular marker; novel; outcome forecast; prevent; prospective; public health relevance; screening; trait

 DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with poor survival, limited treatment options and no known cure. Early detection and treatment is a promising approach that could potentially improve clinical outcomes of patients affected with this devastating disease. Cigarette smoking is the most important environmental risk factor for the development of ILD; we have recently shown that smokers without a prior diagnosis of ILD have radiographic interstitial lung abnormalities (ILA) that are associated with physiologic, functional and molecular changes. Although these findings suggest that a subset of smokers with subclinical ILD will progress to develop clinically significant pulmonary fibrosis, large prospective longitudinal studies are required to define clinical and molecular features associated with subclinical ILD in smokers. In this proposal we will prospectively study a large cohort of smokers enrolled in the Pittsburgh Lung Screening Study (PLuSS). We aim to define clinical and molecular determinants that predict development and longitudinal progression of ILA detected by computed tomography over a 10-year mean follow-up period. We hypothesize that select clinical and molecular features that portend a poor prognosis in IPF patients predict development and progression of subclinical ILD in smokers. To test this hypothesis we will address the following specific aims: Specific Aim 1: Determine prevalence and long-term longitudinal progression of subclinical ILD in smokers enrolled in PLuSS. Specific Aim 2: Define clinical and molecular determinants that predict progression of subclinical ILD in smokers. Specific Aim 3: Identify clinical and molecular determinants that predict the development of subclinical ILD in smokers. The successful completion of this research will provide us with a better understanding of the characteristics and natural history of subclinical ILD and novel non- invasive ways to identify smokers at risk for progression of subclinical ILD.

 描述（由适用提供）：特发性肺纤维化（IPF）是一种慢性进行性肺部疾病，生存率较差，治疗方法有限，没有已知的治愈方法。早期检测和治疗是一种有希望的方法，可以潜在地改善患有这种毁灭性疾病的患者的临床结果。吸烟是ILD发展的最重要的环境风险因素。我们最近表明，没有事先诊断ILD的吸烟者具有与生理，功能和分子变化有关的射线学间隙异常（ILA）。尽管这些发现表明，具有亚临床ILD的吸烟者将进展以发展临床上显着的肺纤维化，但需要大量的前瞻性纵向研究来定义吸烟者中与亚临床ILD相关的临床和分子特征。在此提案中，我们可能会研究参加匹兹堡肺部筛查研究（PLUSS）的大量吸烟者。我们旨在定义临床和分子确定词，以预测在10年的平均随访期内通过计算机断层扫描检测到的ILA的发展和纵向进程。我们假设某些临床和分子特征预示了IPF患者预后不良的预后预测吸烟者中亚临床ILD的发展和进展。为了检验这一假设，我们将解决以下特定目的：具体目标1：确定在Pluss入学的吸烟者中亚临床ILD的患病率和长期纵向进程。具体目标2：定义预测吸烟者亚临床ILD进展的临床和分子决定剂。特定目的3：确定预测吸烟者亚临床ILD发展的临床和分子决定剂。这项研究的成功完成将使我们更好地了解亚临床ILD和新型非侵入性方法的特征和自然历史，以识别有亚临床ILD进展风险的吸烟者。