Proteomic markers of early and late stage pulmonary fibrosis

PROJECT SUMMARY Interstitial lung disease (ILD) is a chronic respiratory illness that can progress to a fibrotic subtype with ongoing aberrant wound healing that occurs in the lung’s epithelium, dysregulated collagen deposition, and architectural distortion that impairs the alveolar-capillary barrier. The most common type of fibrotic ILD is idiopathic pulmonary fibrosis (IPF) which has a poor median survival and is a major reason for lung transplantation. Drugs that are currently approved for IPF slow disease progression but have significant side effects that can make them poorly tolerated by patients. Majority of IPF clinical trials have tested therapies in patients who already have a significant burden of fibrosis in the lungs. To have a significant impact on attenuating disease progression, there is a need to identify novel and tolerable therapies for IPF at all disease stages, from early to late stage. A major step forward to testing therapies that prevent IPF is identifying individuals at higher risk of developing disease. It should be non-invasive assessments that (1) have minimal harm in humans, (2) can identify those at risk of developing IPF, and (3) identify those with a more progressive form of IPF that would benefit from earlier therapeutic interventions. By addressing this major knowledge gap, it will facilitate clinical trial enrichment and ensure adequate power to effectively test drugs and risk factor mitigation aimed at prevention. Our group has identified plasma proteomic biomarkers that perform excellently at predicting survival in IPF. Many of these proteins also associate with subclinical radiological markers of lung injury and fibrosis in non-diseased adults, and thus are promising markers that can be used to identify individuals at risk of developing pulmonary fibrosis. We propose to: (Aim 1) identify and validate proteomic biomarkers that are predictive of worse short-term survival in IPF, (Aim 2) test whether plasma proteomic biomarkers are predictive of future pulmonary fibrosis risk in non-diseased adults, and (Aim 3) identify molecular features of early and later stages of pulmonary fibrosis by incorporating multiple omics platforms in blood and lung tissue samples. Accomplishing the aims of this proposal will identify blood-based proteomic biomarkers that can be used to identify at-risk adults and enroll in preventative clinical trials.