Idiopathic pulmonary fibrosis a fibrotic interstitial lung disease characterized by a median survival of 3-5 years post-diagnosis but exhibits heterogeneous longitudinal disease progression. Recent studies of novel agents confirm beneficial effects on longitudinal change in forced vital capacity but inconsistent benefits on clinical endpoints or health status. Both agents are difficult to tolerate and are likely to be prohibitively expensive. Conducting clinical trials to assess clinical endpoints requires that larg numbers of patients are enrolled and followed for a sufficient period of time. The inability to rapidly recruit sufficient numbers of IPF patients means that many key clinical questions have not been addressed. Restrictive inclusion criteria ensure that patients enrolled in clinical trials often differ from those seen in clinical practice. There remains a critical need to use innovative, pragmatic study designs to identify well tolerated and inexpensive therapies which improve clinical outcomes in patients with IPF. Our group was the first to identify that an abnormal lung microbial community is independently associated with disease progression in IPF subjects. Additional preliminary data link this to a circulating gene expression signature of altered host response. Intriguingly, one investigative group has suggested improved clinical outcomes in IPF patients treated with trimethoprim/ sulfamethoxazole compared to a matched placebo. The totality of these data suggests that an abnormal lung microbiome interacting with genetic susceptibility in host response may be associated with impaired clinical outcomes in IPF. Our principal hypothesis is that antimicrobial therapy in IPF patients will improve clinical outcomes. Our long-term goal is to define patient-specific therapy in IPF. Using a pragmatic trial design CleanUP-IPF will remove many of the known obstacles to clinical trial enrollment in order to recruit a patient population that is highly representative of those seen in clinical practice. We anticipate demonstrating that: 1) a large, pragmatic study in IPF is feasible and will identify clinically meaningful endpoints beyond FVC; 2) anti- microbial therapy will improve clinical outcomes; and 3) genetically predisposed patients will experience differential response to therapy. CleanUP-IPF will revolutionize future studies in IPF and provide data that will alter therapeutic guidelines.

Public Health Relevance

We propose a large, a simple, pragmatic study testing whether a simple, well-tolerated antibiotic improves clinical disease progression in IPF patients. Successful conclusion of our study will dramatically alter future therapeutic development, prove paradigm changing, and provide a platform for precision medicine.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZHL1-CSR-I (M1))
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Punturieri, Antonello
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Weill Medical College of Cornell University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Ryerson, Christopher J; Corte, Tamera J; Lee, Joyce S et al. (2017) A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease. An International Working Group Perspective. Am J Respir Crit Care Med 196:1249-1254
Martinez, Fernando J; Chisholm, Alison; Collard, Harold R et al. (2017) The diagnosis of idiopathic pulmonary fibrosis: current and future approaches. Lancet Respir Med 5:61-71
Kaner, Robert J; Brown, Kevin K; Martinez, Fernando J (2017) AJRCCM: 100-Year Anniversary. Progress in Interstitial Lung Disease. Am J Respir Crit Care Med 195:1104-1107
Huang, Yong; Ma, Shwu-Fan; Espindola, Milena S et al. (2017) Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 196:208-219
O'Dwyer, David N; Norman, Katy C; Xia, Meng et al. (2017) Erratum: The peripheral blood proteome signature of idiopathic pulmonary fibrosis is distinct from normal and is associated with novel immunological processes. Sci Rep 7:46860