Idiopathic pulmonary fibrosis (IPF), the most common and severe interstitial lung disease (ILD), is minimally responsive to current medical therapies, and has a mortality rate comparable to that of many end-stage malignancies. There is increasing awareness that IPF may transition through an asymptomatic stage where the primary detectable abnormalities are radiologic. It is our belief that risk factor modification and medical therapies, when instituted at an early stage, will lead to improved care for patients at risk to develop IPF. However, for this field to progress it will be imperative to develop comprehensive clinical, radiologic, physiologic, and molecular profiles to determine which subjects are at greatest risk to develop pulmonary fibrosis. Recently we demonstrated that smokers with interstitial lung abnormalities (ILA) on chest computed tomography (CT), who had not been previously diagnosed with ILD, had reduced total lung capacity, exercise capacity, and emphysema compared to smokers without ILA. We hypothesize that some of these subjects with ILA are at increased risk to develop IPF. To pursue our hypothesis we will capitalize on existing chest CTs, histopathologic, and genotypic data from large well-phenotyped cohorts. This proposal has the following Specific Aims:
Aim 1) We will identify the clinical predictors of ILA and ILA progression utilizing both the COPDGene and Framingham Heart Study cohorts;
Aim 2) Using a Brigham and Women's Hospital cohort of subjects with both preoperative chest CTs and lung tissue specimens we will determine the correlation between ILA and histopathologic evidence of interstitial pneumonitis/pulmonary fibrosis and;
Aim 3) we will evaluate the genetics and epigenetic correlations between ILA and IPF utilizing the above cohorts.
Idiopathic pulmonary fibrosis (IPF), a disorder characterized by lung scarring, is not responsive to current medical therapies, and has a prognosis comparable to that of many end-stage malignancies. Identifying an early/asymptomatic stage of IPF may lead to improved care for these patients. This proposal will characterize large groups of subjects who may be at risk to develop IPF, identify the environmental, genetic, and epigenetic factors that may increase this risk, and evaluate if these factors are linked to those of patients with IPF.
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