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Principal Investigator: Jeffrey Andrew Sparks
Organization: BRIGHAM AND WOMEN'S HOSPITAL
Fiscal Year: 2024
Award: $732,797
Funding agency: National Heart Lung and Blood Institute
PROJECT SUMMARY / ABSTRACT
Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.5 million people in the
United States. Although parenchymal lung disease, which encompasses interstitial lung disease (ILD) and
emphysema, is a common lung complication of RA with increasing prevalence and mortality, no strategies
currently exist for early detection or risk stratification of progressive disease. This is an area of unmet need that
could lead to improved opportunities for intervention and a decrease in the considerable morbidity and
mortality of RA-associated parenchymal lung disease.
In this proposal, we aim to fully characterize early parenchymal lung disease in RA and establish risk
factors for progressive disease. We hypothesize that clinical and molecular risk factors can predict the
development and progression of RA-associated parenchymal lung disease, including preclinical ILD (preILD)
and emphysema, and that the molecular profile of progressive RA-preILD will overlap with fibrotic RA-ILD. To
test this hypothesis, we will propose the following: In Specific Aim 1, we will determine the prevalence and
progression of RA-associated preILD and emphysema using visual and objective radiologic approaches and
correlate these measurements with functional capacity, respiratory symptoms, and health-related quality of life
assessments. In Specific Aim 2, we will define clinical and molecular determinants that predict the
development and progression of RA emphysema and compare the molecular profile of emphysema with
preILD to provide mechanistic insight into the divergent patterns of parenchymal lung injury caused by RA. In
Specific Aim 3, we will demonstrate that progressive RA-preILD and fibrotic RA-ILD have similar molecular
signatures, suggesting phenotypic and mechanistic overlap. To achieve the aims of this proposal, a
longitudinal cohort of 200 RA patients without a history of ILD will be followed for up to 6 years with detailed
clinical, functional, radiologic, and molecular phenotyping.
The successful completion of this research will provide us with a better understanding of the early
characteristics and natural history of RA-associated ILD and emphysema and establish novel non-invasive
ways to identify those at risk for progressive disease. This will enable closer monitoring and earlier
opportunities for intervention, potentially leading to decreased morbidity and mortality in individuals afflicted
with RA-associated parenchymal lung disease.
Terms: <21+ years old><Accounting><Active Follow-up><Activities of Daily Living><Activities of everyday life><Address><Adult><Adult Human><Affect><Airway Disease><Area><Atrophic Arthritis><Autoimmune Status><Autoimmunity><Biological Markers><COPD><Cause of Death><Cessation of life><Characteristics><Chronic><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><Clinical><Complication><Data><Death><Development><Disease><Disorder><Early Diagnosis><Early Intervention><Early identification><Emphysema><Expression Signature><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profile><Gene Expression Profiling><General Radiology><Groups at risk><Health Status><High Prevalence><History><Hospital Admission><Hospitalization><Individual><Inflammation><Inflammatory><Injury><Interstitial Lung Diseases><Intervention><Intervention Strategies><Knowledge><Level of Health><Literature><Long-term cohort><Longitudinal cohort><Longterm cohort><Lung><Lung Diseases><Lung Respiratory System><Lung damage><MG1><MUC5B><MUC5B gene><Measurement><Measures><Methods><Molecular><Molecular Fingerprinting><Molecular Profiling><Monitor><Morbidity><Morbidity - disease rate><Natural History><Outcome><Patients><Pattern><People at risk><Persons><Persons at risk><Phenotype><Physiologic><Physiological><Populations at Risk><Predisposition><Prevalence><Progressive Disease><Publishing><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Emphysema><Quality of Life Assessment><RNA Seq><RNA sequencing><RNAseq><Radiology><Radiology Specialty><Recording of previous events><Research><Respiratory Signs and Symptoms><Rheumatoid Arthritis><Risk><Risk Factors><Scoring Method><Smoking><Stress><Susceptibility><Testing><Time><Transcript Expression Analyses><Transcript Expression Analysis><United States><Usual Interstitial Pneumonia><Usual Interstitial Pneumonitis><Variant><Variation><Visual><Work><active followup><adulthood><airway symptom><analyze gene expression><bio-markers><biologic marker><biomarker><biomarker discovery><biomarker signature><chronic obstructive pulmonary disorder><clinical phenotype><clinical risk><daily living function><daily living functionality><developmental><disease of the lung><disorder of the lung><early detection><effective therapy><effective treatment><emphysematous><fibrosing interstitial lung disease><fibrotic interstitial lung disease><fibrotic lung disease><fibrotic pulmonary disease><follow up><follow-up><followed up><followup><functional ability><functional capacity><gene expression analysis><gene expression assay><gene expression pattern><gene expression signature><health level><health related quality of life><high risk><histories><improved><improved outcome><injuries><insight><interstitial><interventional strategy><lung disorder><lung function><lung injury><molecular phenotype><molecular profile><molecular signature><mortality><novel><patient screening><pre-clinical><preclinical><progression risk><pulmonary><pulmonary damage><pulmonary function><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><respiratory symptom><rheumatic arthritis><risk stratification><stratify risk><transcriptional profile><transcriptional profiling><transcriptional signature><transcriptome sequencing><transcriptomic sequencing>