Pulmonary, Critical Care and Sleep Disorders Medicine

Faculty in the Division of Pulmonary, Critical Care and Sleep Disorders Medicine are engaged in sophisticated research in animal models and in humans that seeks to identify ways in which to intervene to prevent, reverse or halt the progression of lung disease.

Armed with multiple models, investigators in the division are testing the mechanisms that lead to lung inflammation and fibrosis. They are also testing pathways that mediate lung rejection after lung transplantation.

In human studies, the group is exploring the effectiveness and safety of drugs useful in the management of pulmonary disorders like Idiopathic Pulmonary Fibrosis, COPD, asthma, and obstructive sleep apnea.

Studies are also being conducted in the intensive care units to target pneumonia and other critical care illnesses.  Together, this talented group of physician-scientists and investigators, are involved in world-class investigations that are expected to unveil important new treatments for the management of the millions of Americans suffering from pulmonary disease.

► R01 HL64894-05: "The regulation and Function of EC-SOD"

Sponsor: NIH/NHLBI

PI: Rodney Folz, M.D., Ph.D.

• The major goal of this project is to elucidate the genomic organization of the EC-SOD in the mouse and to determine lung specific transcriptional regulatory components and the function of the EC-SOD in the murine lung.

► ADC113874: "A Randomized, Double-Blinded, Parallel Group, Multicenter Study of the Effects of Fluticasone Propionate/Salmeterol Combination Product 250/50mcg BID (Advair Diskus) in Comparison to Salmeterol 50mcg (Serevent Diskus) on the Rate of Exacerbations of Chronic Obstructive Pulmonary Disease (COPD) Following Hospitalization"

Sponsor: Glaxo Smith Kline (Pending)

PI: Rodney Folz, M.D., Ph.D.

• This is a randomized, double-blinded, parallel-group, multicenter study to be conducted in the United States and other countries. The purpose of the study is to evaluate the rate of exacerbations of chronic obstructive pulmonary disease (COPD) following hospital discharge for an acute exacerbation of COPD, in patients receiving either fluticasone propionate/salmeterol combination product 250/50mcg BID or Salmeterol 50mcg BID via Diskus over 29 weeks.

► HZC113782: "A Clinical Outcomes Study to compare the effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg with placebo on Survival in Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) and a history of or at increased risk for cardiovascular disease"

Sponsor: Glaxo Smith Kline (Pending)

PI: Rodney Folz, M.D., Ph.D.

• This is a randomized, double-blind, parallel-group, multi-center, placebo-controlled study to evaluate the long term efficacy and safety of FF/VI Inhalation powder 100/25mcg QD, FF Inhalation powder 100mcg QD and VI Inhalation powder 25mcg QD when administered via the Novel Dry Powder Inhaler.

► Clinical Protocol AST-111: "Evaluation of Novel Biomarkers from Acutely Ill Patients at Risk for Acute Kidney Injury"

Sponsor: Astute Medical, Inc.

PI: Mohamed Saad, M.D.

• The objective of this multicenter prospective cohort study is to collect blood and urine samples that may help identify and validate novel biomarkers from acutely ill patients for the early detection and risk assessment of acute kidney injury (AKI). The study is observational and will have no impact on the medical management of the patient.

► CA-ALT-836-01-08: "Efficacy and Safety Evaluation of ALT-836 in Patients with Sepsis and Acute Lung Injury/Acute Respiratory Distress Syndrome"

Sponsor: Altor Bioscience Corporation

PI: Mohamed Saad, M.D.

• This is a prospective, randomized, double-blind, multi-center, Phase II clinical study of ALT-836 versus placebo in patients with sepsis and acute lung Injury/acute respiratory distress syndrome.

► REDOXS: "Reducing Deaths due to Oxidative Stress"

PI: Mohamed Saad, M.D.

• The purpose of this study is to find out if giving Glutamine and antioxidant supplements to critically ill patients will improve their chances of survival.

► SABR: "Sleep Apnea Biomarker Research"

PI: Fidaa Shaib, M.D.

• The purpose of the study is to clinically validate the application of the ELISA assay for urocortin 3 protein in the diagnosis of sleep apnea in children and adults by testing urine samples collected before and after sleep from 200 children and 200 adults.

► "A Phase One, Open Label, Multi-Dose Study to Evaluate the Safety, Tolerability, and Biologic Effects of Three Doses of IW001 in Patients with Idiopathic Pulmonary Fibrosis (IPF)"

Sponsor: ImmuneWorks Inc.

PI: Jesse Roman, M.D.

• The basis for this study rests on the hypothesis that exposure of collagen V, normally "buried" inside the protein matrix of the lung promotes the progression of fibrosis in IPF. The effects of collagen V exposure on pulmonary fibrosis are most likely greatest in individuals with antibodies against this collagen. Subjects with IPF and antibodies to collagen V will be enrolled and given the collagen V compound, IW001, orally with the goal to produce immune tolerance to this collagen. As a phase one trial, this study will not address the efficacy of IW001 on slowing or stopping pulmonary fibrosis, but will address important dosing, safety, and tolerability aspects for future efficacy trials. How the compound interacts with the immune system and other biological properties will also be addressed.

► "A Phase 2, Sequential, Ascending Dose Study to Characterize the Safety, Tolerability, Pharmacokinetic and Biological Activity of CC-930 in Idiopathic Pulmonary Fibrosis (IPF)"

Sponsor: Celgene

PI: Rafael Perez, M.D.

• This study is based on the inhibition of an important cell signaling pathway that is likely involved in the promotion of fibrosis. The main purpose of the study is to establish safety and tolerability of the agent in patients with IPF.

► "A phase III multicenter, 52-week treatment, randomized, double-blind, parallel group, active controlled study to evaluate the effect of QVA149 (110/50 mcg) vs. NVA237 (50 mcg) and open-label tiotropium (18 mcg) on COPD exacerbations in patients with severe to very severe COPD"

Sponsor: Novartis

PI: Rafael Perez, M.D.

• This is an efficacy study with the primary objective to determine if compound QVA149 (a combination of the long acting beta-agonist, indacaterol, and the long-acting muscarinic inhibitor, glycopyrronium) is superior to NVA237 (glycopyrronium) or open-label tiotropium in decreasing the rates of acute exacerbations in subjects with severe COPD.

► "Prednisone, Azathioprine, N-Acetylcysteine: A Study That Evaluates Response in Idiopathic Pulmonary Fibrosis (PANTHER-IPF)"

Sponsor: NIH/NHLBI

PI: Jesse Roman, M.D.

• This study centers on whether or not N-acetylcysteine (NAC) alone, or in combination with prednisone and azathioprine, mitigates the progression of IPF. Individuals with IPF are randomized into receiving the three agent combination, NAC alone, or placebo.  The primary outcome measure is change in the forced vital capacity over 60 weeks. Secondary measures assess other parameters of disease progression and, importantly, the number of acute exacerbations of IPF.

► "Anticoagulant Effectiveness in Idiopathic Pulmonary Fibrosis (ACE-IPF)"

Sponsor: NIH/NHLBI

PI: Jesse Roman, M.D.

• This study is based on the relationships between the biology of coagulation and fibrosis as well as observations that anticoagulation may slow the progression of pulmonary fibrosis.  The time to the composite endpoint consisting of time to death, acute exacerbations/respiratory-related hospitalizations, and drop in FVC ≥ 10% predicted, is the primary outcome.

► "Airway sensors with myelinated afferents"

Sponsor: VA Merit Review

PI: Jerry Yu, M.D., Ph.D.

• The major goal of this project is to elucidate the mechanisms of signal trasduction in the airway sensory receptors. This is important for understanding the lung-brain communication.

► R03 HL097012: "Vitamin D status in pulmonary fibrosis"

Sponsor: NIH/NHLBI

PI: Allan Ramirez, M.D.

• In this project, archived human lung and blood samples from subjects with severe idiopathic pulmonary fibrosis obtained from the NHLBI-funded Lung Tissue Research Consortium will be analyzed for Vitamin D content and expression of Vitamin D signaling/metabolizing proteins.

► K08 HL077533: "The role of Smad3 in obliterative bronchiolitis"

Sponsor: NIH/NHLBI

PI: Allan Ramirez, M.D.

• The goals of this project are to delineate the mechanisms by which cysteine-cystine oxidation, matrix-cell interactions, and PPARg activity modulate the Smad3 signaling pathways that lead to the fibrotic phenotype.

► 09BGIA2060109: "Vitamin D in lung fibrosis"

Sponsor: American Heart Association

PI: Allan Ramirez, M.D.

• This project utilizes animal and cellular models of lung fibrosis to characterize the role of Vitamin D signaling on TGFb/Smad3 pro-fibrotic pathways.