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New England Journal of Medicine Publishes Pitt/UPMC Study Finding Potential Asthma Treatment

Posted by andrewsj3 on Tuesday, May 21st 2013     

Gladwin, Kaminski, Student Research Receive Honors at International Pulmonology Conference

PITTSBURGH, May 21, 2013 – An experimental, lab-made molecule was able to stick to certain inflammatory proteins and reduce acute breathing problems among people with a type of moderate-to-severe asthma, according to researchers at the University of Pittsburgh School of Medicine. Their findings were published today in the New England Journal of Medicine, coinciding with their presentation of the study in Philadelphia at the annual meeting of the American Thoracic Society.
Recent estimates suggest that 24.6 million Americans have asthma, and 10 to 20 percent of them don’t have optimal control of their symptoms despite modern medications, said senior author Sally Wenzel, M.D., professor, Division of Pulmonary, Allergy and Critical Care Medicine (PACCM), Pitt School of Medicine, and director, University of Pittsburgh Asthma Institute at UPMC/University of Pittsburgh School of Medicine. Effective treatment of persistent, moderate-to-severe asthma has been challenging.
“We suspect that there are different underlying causes that lead to the clinical syndrome of asthma, so different treatment approaches are likely needed depending on what type of asthma a patient has,” she said. “A one-size-fits-all strategy might not, in fact, work for everyone.”
For the Phase IIa trial, the researchers assessed asthma patients who: were taking moderate to high doses of inhaled steroids and airway-opening drugs called long-acting beta agonists; and had high counts of eosinophils, a kind of white cell usually associated with allergy. For 12 weeks, 52 participants received weekly injections of a placebo and 52 others received weekly injections of dupilumab, a monoclonal antibody that inhibits the activity of signaling molecules involved in inflammation. After four weeks, both groups stopped using their long-acting beta agonist. Between the sixth and ninth weeks, they gradually stopped taking the inhaled steroid.
Three patients in the dupilumab group (5.8 percent) had asthma attacks compared to 23 (44.2 percent) in the placebo group, a reduction of 87 percent. The experimental agent was associated with lower levels of biomarkers of inflammation. Minor irritation at the injection site and of the nose and throat, headache and nausea occurred more frequently in the dupilumab group.
“Our findings suggest that dupilumab holds promise for the treatment of moderate-to-severe asthma,” Dr. Wenzel said. “However, further studies are needed to better define the patients who will do the best with this new approach, as well as longer-term efficacy and safety.”
Added Mark Gladwin, M.D., chief of PACCM: “A major focus of our Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh is personalized or precision medicine, which aims to match a specific treatment to a specific disease, the right approach for the right person. This study highlights the potential of targeting specific molecular pathways in the right patient with asthma.”
The study team included other researchers from the University of Pittsburgh; Colorado Allergy and Asthma Centers, Denver, CO; California Allergy & Asthma Medical Group, Inc., Los Angeles; Peninsula Research Associates, Rolling Hills Estates, CA; Research and Development, Sanofi, Bridgewater, NJ; and Regeneron Pharmaceuticals, Inc., Tarrytown, N.Y.
The project was funded by Sanofi and Regeneron.
Sally Wenzel, M.D., talks about her asthma research published today by the New England Journal of Medicine and presented concurrently at the national convention of the American Thoracic Society

Gladwin, Kaminski Awards

The American Thoracic Society, at its International Conference 2013 Awards Session in Philadelphia on Sunday, May 19, presented 12 awards to the leading pulmonology clinicians and researchers. Two of its four honorees for Recognition for Scientific Accomplishments are leaders from the Pitt/UPMC PACCM programs.
Mark Gladwin, M.D., PACCM chief, and director, Pitt’s Vascular Medicine Institute, and Naftali Kaminski, M.D., professor and director,Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases at UPMC, received the scientific awards in a rare 1-2 for a single institution or city. The other winners included Paul Noble, M.D., chair of the Department of Medicine, Cedars-Sinai Medical Center in Los Angeles, and Timothy Blackwell, M.D., director of PACCM, Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Honor for Pitt Student’s Research

In a study highlighted at the American Thoracic Society annual meeting, Pitt researchers linked systemic inflammation in chronic obstructive pulmonary disease (COPD) with depression.
For the project, 450 tobacco-exposed patients were given a variety of depression and COPD tests. The researchers found that 49 of 215 (22.8 percent) female participants and 37 of 235 (15.7 percent) of male participants were depressed. Depressive symptoms were most strongly associated with: higher levels of interleukin-6, a biomarker of systemic inflammation; lower than expected forced expiratory volume, which is the maximal amount of air that can be exhaled in one second; female sex; and current smoking status.
“Depression has been linked with a number of symptoms and co-morbidities in COPD patients,” said student researcher Hilary Strollo, M.S., a graduate of Pitt’s School of Health and Rehabilitation Sciences, who is set to present this research project at the meeting at 3:15 p.m., Wednesday, May 22. “Our findings add evidence of a strong relationship between depression and one of the hallmarks of COPD – systemic inflammation – independent of the severity of the disease.”
Ms. Strollo is scheduled to attend an 11:15 a.m. news conference today, May 21, focusing on a handful of research presentations at the annual meeting. The events are held in the Pennsylvania Convention Center in Philadelphia.
ATS contacts are Nathaniel Dunford, 914-815-0503 or ndunford@thoracic.org, and Brian Kell, 516-305-9251 or bkell@thoracic.org. Their press-room telephone numbers are 215-418-2408 and -2409.

 

category: Pulmonology
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UPMC Performs First “Breathing Lung” Transplant on East Coast Using OCS Lung

Posted by andrewsj3 on Wednesday, March 13th 2013     

 PITTSBURGH, March 13, 2013 – UPMC surgeons have performed a “breathing lung” transplant using a portable machine that provides a constant supply of blood and nutrients to the donor organs, which doctors say has the potential to keep them healthier and viable for longer than ever before. 

The double-lung transplant was performed March 4 at UPMC Presbyterian, using the Organ Care System, also known as the OCS lung, by TransMedics Inc. This is the first time the device has been used on the East Coast. The patient, a 53-year-old man from Moundsville, W.Va., had suffered from pulmonary fibrosis and pulmonary hypertension. He was in good condition Wednesday.

Traditionally, donor lungs are cooled and put on ice with no blood circulation, a process that essentially puts them to sleep. Once removed from a blood supply, though, the lungs can deteriorate rapidly, which can lead to complications for the recipient or, in some cases, the determination that the organs are no longer viable. Using the OCS device, the lungs are immediately placed in the machine after donation, where they are kept at body temperature and functioning while in transit to the recipient.

“Unfortunately, many people waiting for an organ transplant die because usable donor organs aren’t available. Using this method, we believe we can help more people and save lives,” said Christian Bermudez, M.D., UPMC’s chief of cardiothoracic transplantation who performed the transplant surgery and principal investigator of a study involving the OCS lung.

UPMC Surgeons hope to enroll 10 patients in the clinical trial, which will randomize five participants to get the OCS device and five to be treated using the traditional method of care. The goal is to assess whether perfusing the lungs in the machine will decrease the chances of early dysfunction of the transplanted organ, thus resulting in better long-term function for the recipient.

“This is an exciting technology breakthrough that has the potential to increase the organ donor pool and improve outcomes for those receiving these specially perfused lungs,” said James Luketich, M.D., chair of the Department of Cardiothoracic Surgery.

The OCS lung machine resembles a small cart on wheels. It can monitor the organ’s arterial pressure, gas exchange ratio, vascular resistance and other data through embedded sensors so doctors can get an immediate snapshot of the organ’s viability.

UPMC has a long history of innovation in transplantation, and surgeons have performed more than 3,000 heart and lung transplants. In 2007, UPMC surgeons were the first in the U.S. to perform a transplant in which a donor heart was maintained in a beating state for two hours and 45 minutes before being implanted into its recipient. That transplant used a similar perfusion machine developed for heart transplantation by TransMedics Inc.

A video with footage from the surgery and an interview with Dr. Bermudez will be available later today on YouTube and on the Inside Life Changing Medicine blog.  

About UPMC’s transplant programs
UPMC’s transplant programs are among the world’s largest and are internationally renowned for their influence on the field of transplantation. For more than 30 years, UPMC has been providing care to adult and pediatric transplant patients through services at the Thomas E. Starzl Transplantation Institute, the UPMC Department of Cardiothoracic Surgery and the Children’s Hillman Center for Pediatric Transplantation. Today, UPMC has performed more than 17,000 transplants, including heart, lung, intestinal, kidney, liver, pancreas and multiple-organ transplants, along with heart assist device implantation. UPMC also partners with the University of Pittsburgh to advance basic science and clinically applied research, as well as to support the teaching and training of transplant specialists worldwide.

category: Lung Transplantation, Pulmonology, Transplantation
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UPMC First to Enroll Patients in Inaugural U.S. Trial Inserting Coils in Emphysema-diseased Lungs

Posted by andrewsj3 on Monday, February 25th 2013     
PITTSBURGH, Feb. 25, 2013 – UPMC is the first center in North America to enroll patients into a Food and Drug Administration-approved clinical trial that will test whether the insertion of small coils can collapse diseased lung areas and improve both lung function and exercise tolerance among patients with advanced emphysema. UPMC pulmonologists on Feb. 21 performed the procedure on a 65-year-old Hampton woman in a newly launched study that aims to recruit 315 patients across 30 U.S. and European centers.
 
The RENEW Lung Volume Reduction Coils provide a minimally invasive alternative to lung volume reduction surgery, which was pioneered by UPMC surgeons and pulmonologists more than a decade ago. Pulmonologists in Europe have been investigating this device for the past four years, but only a large, randomized trial such as this research can medically prove the effectiveness of this intervention, said Frank Sciurba, M.D., principal investigator of the local study arm, director of the UPMC Pulmonary Function and Exercise Physiology Laboratory, and professor, Division of Pulmonology, Allergy and Critical Care Medicine (PACCM), University of Pittsburgh School of Medicine.
 
This trial extends PACCM’s legacy in taking a lead in creating or investigating novel approaches to treating patients with advanced lung disease, said Mark Gladwin, M.D., the division’s chief and the director of Pitt’s Vascular Medicine Institute.
 
“This represents an innovative approach to non-invasively improve the lung function of patients with COPD, unlike prior approaches that required major surgery,” he added.
 
The RENEW trial is funded by the California-based company PneumRx, which developed the device. The coils are small, super-elastic, shape-memory coils made of a metal commonly used in medical implants. In a simple, hour-long procedure employing a bronchoscope, Sciurba and fellow UPMC pulmonologist Maria Crespo, M.D., F.C.C.P., associate medical director, UPMC Lung Transplantation Program, implanted up to 10 coils in wire form into one lung of the patient. The wires recoil after deployment, pulling in the damaged, overinflated lung area so that the healthier, remaining lung can inflate and deflate more effectively, improving airway function and breathing both at rest and during exercise. Four months later, up to 10 coils go into the other lung.
 
Candidates for the trials include patients who have severe emphysema and impaired exercise tolerance after quitting smoking. In the Hampton woman’s case, she gave up cigarettes more than a quarter-century ago.
 
Emphysema is an irreversible, incurable disease where sufferers become progressively less mobile, enduring shortness of breath and increasing discomfort with any activity, to the point of becoming homebound. Current treatments include medicine therapy such as bronchodilators, inhaled steroids and antibiotics. However, such treatments show limited benefits, and patients progress over time to where few options remain, leaving sufferers with a declining quality of life. 
 
“I always ask my patients, ‘What was the last important activity that you had to give up?’ and I consider their answer to be our target for successful treatment,” Dr. Sciurba said. “If the RENEW trial is successful in proving these coils can improve exercise tolerance, we will have an important new tool to offer our patients with advanced emphysema that will help them regain the lost activities so important to their quality of life.”
 
For more information about participating in the trial, emphysema sufferers over the age of 35 who quit smoking at least two months prior should call Christina Ledezma, Ph.D., clinical research coordinator, at 866-948-2673.
category: Pulmonology
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2012 Pittsburgh International Lung Conference

Posted by UPMC Physician Resources on Thursday, August 30th 2012     

The 2012 conference will focus on Acute Lung Injury:  New Mechanisms, Future Therapies, and the Translation to Clinical Care and will be held in Pittsburgh, Pennsylvania, October 5-6, 2012.

This exciting conference aims to provide a forum for the exchange of new and cutting-edge information about ARDS by bringing together leading regional, national, and international experts in the field.

View six presentations from the 2011 conference.

WHO SHOULD ATTEND
The target audience for this conference is critical care and pulmonary physicians, doctors in general medical fields, and allied health professionals (e.g., nurses, nurse practitioners, respiratory therapists).  Because of the emphasis on clinical and scientific investigation, the seminars also will target basic, translational, and clinical investigators with interests in ARDS, pneumonia, and sepsis research, as well as biomedical researchers from around the United States, internationally, and within industry.

ACTIVITY DIRECTORS

Mark T. Gladwin, MD
Division Chief, Pulmonary, Allergy, and Critical Care Medicine
Director, Vascular Medical Center

Rama K. Mallampalli, MD
Professor of Medicine, Cell Biology, and Physiology
Director, Acute Lung Injury Center of Excellence
Chief, Pulmonary Division of VA Pittsburgh Healthcare System

Click here to hear about the conference from the 2012 course directors.

CONTINUING MEDICAL EDUCATION
The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The University of Pittsburgh School of Medicine designates this live activity for a maximum of 14.0 AMA PRA Category 1 Credit(s)™. Each physician should only claim credit commensurate with the extent of their participation in the activity. Other health care professionals are awarded 1.4 continuing education units (CEU’s) which are equal to 14.0 contact hours.

category: Events, Pulmonology

Antibiotic that Works in Low-Oxygen Setting Prevents Reactivation of TB Infection, Says Pitt Team

Posted by andrewsj3 on Monday, July 23rd 2012     
PITTSBURGH, July 23, 2012 – Reactivation of latent tuberculosis infection could be better prevented if a drug that is effective against bacteria in low-oxygen environments is added to the treatment regimen, according to researchers at the University of Pittsburgh School of Medicine in this week’s online Early Edition of the Proceedings of the National Academy of Sciences.
 
Pulmonary TB is spread through infected air droplets, said senior author JoAnne L. Flynn, Ph.D., professor, Department of Microbiology and Molecular Genetics, Pitt School of Medicine. People can develop active TB with cough, fever, night sweats and fatigue, but most develop an asymptomatic “latent” infection where the bacteria, called Mycobacterium tuberculosis, can remain in the lung tissue walled off in a lesion called a granuloma. In some, particularly the elderly or immune-compromised, the infection can reactivate years later.
 
“An estimated 2 billion people worldwide are latently infected with TB, so it’s imperative to have treatment strategies that can prevent the disease from becoming active again,” Dr. Flynn said. “The infection reactivates in about 10 percent of patients with healthy immune systems, and each case of infectious TB can lead to more than seven new cases. ”
 
Currently, active TB that is not resistant to antibiotics is treated with a so-called “short course” of two months of the drugs isoniazid (INH), rifampin (RIF), pyrazinamide and ethambutol, followed by four more months of INH and RIF. Latent infection is treated with nine months of INH, which acts primarily on replicating bacteria. It’s challenging for patients to continue the treatments to their conclusion, so new drugs that act more quickly would be very helpful, noted Dr. Flynn, who also is an associate member of the University of Pittsburgh’s Center for Vaccine Research.
 
Previous research has shown that the TB bacilli that can survive low-oxygen conditions are not susceptible to INH. Yet the caseous (“cheese-like”) granulomas commonly seen in human infection have areas of tissue death, or necrosis, associated with a hypoxic environment. That led the team to examine whether metronidazole (MTZ), an antibiotic that is known to be effective against non-replicating bacteria in low-oxygen settings, would be better able to eradicate the TB bacilli contained in the granuloma.
 
The researchers found that in a macaque model of TB, two months of MTZ alone was as effective as two months of INH and RIF at preventing reactivation of the infection induced by an agent called anti-tumor necrosis factor antibody, which triggered disease in most of the untreated animals. Also, adding MTZ to an INH and RIF regimen reduced bacterial burden in monkeys with active TB within two months.
 
“Instead of merely active or latent, TB can be considered a spectrum of the same disease related to bacterial burden,” Dr. Flynn said. “The next step is to find better drugs that work in these hypoxic areas of granulomas because MTZ can be difficult to tolerate over an extended time.”
 
Co-authors of the paper include Philana Ling Lin, M.D., Children’s Hospital of Pittsburgh of UPMC; Veronique Dartois, Ph.D., Novartis Institute for Tropical Diseases, Singapore; Paul J. Johnston, Department of Microbiology and Molecular Genetics, Pitt School of Medicine; Christopher Janssen, D.V.M., and Edwin Klein, D.V.M., Division of Laboratory Animal Research, University of Pittsburgh; and Laura Via, Ph.D., Michael B. Goodwin, and Clifton E. Barry III, Ph.D., all of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
 
The project was funded by the Bill and Melinda Gates Foundation Grand Challenge 11 “Drugs for Latent TB”; the Otis Foundation; and, in part, by the Intramural Research Program of NIAID.
category: Pulmonology
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Pitt Team Finds New Type of Severe Asthma, Can Be Treated with Drugs that Suppress the Immune System

Posted by andrewsj3 on Wednesday, July 18th 2012     
PITTSBURGH, July 18, 2012 – Researchers at the University of Pittsburgh School of Medicine have identified a subset of severe asthma that improves with drug regimens that suppress the immune system. In the American Journal of Respiratory and Critical Care Medicine, they dubbed the condition “asthmatic granulomatosis” after the characteristic small areas of focal inflammation that can be found in the lungs of those who have it.

 Five to 10 percent of patients with asthma have disease that can be classified as severe, meaning it is difficult to treat and often causes life-threatening breathing problems, said lead author Sally E. Wenzel, M.D., professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, and director of the University of Pittsburgh Asthma Institute at UPMC and the University of Pittsburgh School of Medicine. Typically these patients are treated with the aim of reducing lung inflammation, but treatment often leads to devastating consequences due to steroid side effects.

“We’re now learning that all severe asthma is not the same, but is in fact the result of different problems,” she said. “If we better understand the underlying mechanisms that are causing the symptoms, we can offer better treatments.”

 For the study, the team examined a group of patients with severe asthma who were being treated at the Difficult Asthma Clinic at the UPMC Comprehensive Lung Center during a four-year period. Each of the patients met with a certified asthma educator; were taking high doses of inhaled steroids, with or without ingested steroids; and had been monitored for three to 24 months to optimize therapy.

Nineteen patients then underwent biopsies of their lung tissue using a video-assisted, fiberoptic scope. Ten of them not only had airway changes typical of asthma, but also lesions called granulomas, which are nodules of inflammation sometimes seen with certain infections or with autoimmune diseases. None of the patients had a history of hypersensitivity pneumonitis, an acute illness caused by inhalation of foreign particles such as dust, molds and fungi, which can also lead to granuloma formation.
 
However, 70 percent of the patients had a personal or family history of autoimmune-like disease such as lupus and rheumatoid arthritis. Because granulomas can be produced by an over-active immune system, the team treated the 10 cases with drugs that suppress it, including azathioprine, mycophenolic acid, methotrexate or infliximab. Nine of them reduced their steroid doses and had improvements in standard lung-function tests while one has experienced difficulty tolerating the powerful immune-suppressants.
 
Of the other nine patients who had biopsies, six had tissue changes that reflected asthma, but no granulomas, and three had other issues, including indications of aspiration, pneumonia and small blood clots.
 
“The unexpected finding of granulomas in a subset of patients with severe asthma warrants approaching it as a newly described disease, which we’ve named asthmatic granulomatosis,” Dr. Wenzel said. “It is a condition that has overlapping features of asthma, autoimmunity and granulomas, and it appears to respond better to immune-suppressants than to high-dose steroid treatment.”
 
Asthma specialists should consider getting tissue biopsies in atypical severe asthmatics, the researchers said. More research is needed to determine the immunological pathways that contribute to the disease and develop biomarkers that will simplify diagnosis of asthmatic granulomatosis, they added.
 
“These studies advance our division’s focus on precision, or personalized, medicine — an effort to better refine specific patient diagnoses and tailor more effective therapies,” said Dr. Mark T. Gladwin, chief of the Pulmonary, Allergy and Critical Care Medicine Division.
 
Co-authors include Catherine Vitari, B.S., R.N., Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine; Manisha Shende, M.D., Department of Surgery; Diane C. Strollo, M.D., Department of Radiology; Allyson Larkin, M.D., Department of Pediatrics; and Samuel A. Yousem, M.D., Department of Pathology, all at the University of Pittsburgh School of Medicine.
 
The project was funded by the Dellenback Research Fund.
category: Pulmonology
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UPMC Clinches Top-Ten Spot on U.S. News & World Report Honor Roll of America’s Best Hospitals

Posted by andrewsj3 on Tuesday, July 17th 2012     

PITTSBURGH – UPMC rose to 10th place in U.S. News & World Report’s annual Honor Roll of America’s Best Hospitals – making it the highest-ranked medical center in Pennsylvania. U.S. News & World Report ranked UPMC first in the state and first in Pittsburgh.

“This national recognition is a testament to the skill and dedication of our physicians, nurses and staff and to the superb care they provide every day at UPMC. Our patients and our community have come to expect this level of excellence and we are committed to assuring we deliver. Our proudest achievements come when we make a difference in the lives and health of our patients,” said Elizabeth Concordia, executive vice president of UPMC and president of the Hospital and Community Services Division. “When patients require care, the choice is clear; the nation’s best care is here at UPMC.”

Nationally, UPMC is ranked for excellence in 15 adult specialty areas and is among the top 10 in nine specialty areas: Ear, Nose & Throat; Gastroenterology; Geriatrics; Gynecology; Nephrology; Neurology and Neurosurgery; Orthopaedics; Psychiatry and Pulmonology.

Last month, U.S. News named its 2012 Honor Roll of America’s Best Children’s Hospitals, on which Children’s Hospital of Pittsburgh of UPMC ranked ninth. This year marks UPMC’s 13th appearance on the Honor Roll. Last year, the list placed UPMC 12th nationally.

“A stellar ranking such as this validates what we know to be true – that UPMC is one of the very few academic medical centers in the nation that brings together the best in patient care, top-notch facilities and superior scientists,” added Steven Shapiro, M.D., senior vice president and chief medical and scientific officer, UPMC. “The exceptional clinical services that UPMC provides, fortified by Pitt’s academic research, work hand-in-hand to help us care for patients when they need us.”

About UPMC

UPMC is a $10 billion global health enterprise with more than 55,000 employees headquartered in Pittsburgh, Pa., and is transforming health care by integrating more than 20 hospitals, 400 doctors’ offices and outpatient sites, a health insurance services division, and international and commercial services. Affiliated with the University of Pittsburgh Schools of the Health Sciences, UPMC is redefining health care by using innovative science, technology and medicine to invent new models of accountable, cost-efficient and patient-centered care. For more information on how UPMC is taking medicine from where it is to where it needs to be, go to UPMC.com.

category: Gastroenterology, Geriatrics, Gynecology, Neurology, Neurosurgery, Orthopaedic Surgery, Otolaryngology, Psychiatry, Pulmonology, UPMC
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Pitt Researchers Awarded $8.3 Million NIH Grant to Study Sarcoidosis, Alpha-1 Antitrypsin Deficiency

Posted by andrewsj3 on Wednesday, June 27th 2012     
PITTSBURGH, June 27, 2012 – A multidisciplinary team at the University of Pittsburgh will be leading a national effort to explore the relationships between the bacteria that live in the lungs, gene activation patterns, and disease progression. The project aims to learn more about the causes and progression of two potentially deadly yet under-studied lung diseases, alpha-1 antitrypsin (A1AT) deficiency and sarcoidosis, as well as possibly to identify new treatments for them.
 
Funded by a three-year, $8.3 million grant from the National Institutes of Health, the Genomic Research in A1AT and Sarcoidosis study (GRADS) Genomics and Informatics Center will obtain patient samples from seven clinical centers across the nation and use a combination of sophisticated genome and microbiome profiling techniques with advanced computational methods to identify  biomarkers that indicate the current status of the lung diseases and predict their progression and response to the therapy, explained lead-principal investigator Naftali Kaminski, M.D., professor, Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, and director, Dorothy P. and Richard P. Simmons Center for Interstitial Lung Disease.
 
“Integrating genome, microbiome and clinical information has never been done in sarcoidosis or A1AT,” he said. “The insights from this study may dramatically change the understanding and management of both diseases.”
 
Co-principal investigator Michael Becich, M.D., Ph.D., professor and chair, Department of Biomedical Informatics, Pitt School of Medicine, noted that the study team included experts in genomics, pulmonary medicine, epidemiology, medical bioinformatics, computer science, quantitative imaging, computational biology, sequencing, and microbiome and virome research.
 
“This coordinated, multidisciplinary effort will ensure that data are not only obtained, but also analyzed and shared with the scientific community,” he said.
 
“This study is an important step toward implementing personalized medicine approaches in chronic lung disease,” added co-principal investigator Stephen R. Wisniewski, Ph.D., professor, Department of Epidemiology, and associate dean for research, Graduate School of Public Health, University of Pittsburgh.
 
The GRADS program is sponsored by the NIH’s National Heart, Lung, and Blood Institute (NHLBI).
 
“This award highlights the commitment of the NHLBI to use cutting-edge molecular and genomics applications for the discovery of disease biomarkers to identify new diagnostic tools and targets for new therapies,” said James Kiley, Ph.D., director of the NHLBI Division of Lung Diseases. “It also underscores the NHLBI’s commitment to advance understanding of all lung diseases.”
 
In one of two projects, the researchers will use samples collected by GRADS centers to examine the hypothesis that changes in the microbial environment, or microbiome, of the lung influence the severity of A1AT deficiency, an inherited disorder in which the body does not make sufficient amounts of the A1AT protein leading to early lung and liver disease. The researchers also hope to find biomarkers of disease status in the sputum.
 
The second project will explore whether shifts in immune regulation and in the microbiome population can indicate and predict the severity of sarcoidosis, a disorder of uncontrolled inflammation that can affect any organ, but typically starts in the lungs, skin and lymph nodes and is characterized by a highly variable and unpredictable course.
 
Kevin Gibson, M.D., professor, University of Pittsburgh Division of Pulmonary, Allergy and Critical Care Medicine, and clinical director of the Simmons Center, is the principal investigator of the local GRADS clinical center.
 
Other collaborating and clinical GRADS centers include Vanderbilt University; University of South Carolina; University of California, San Francisco; University of Illinois at Chicago; Yale University; the J. Craig Venter Institute; University of Pennsylvania; National Jewish Health; and Johns Hopkins University.
 
The GRADS genomics and informatics center is funded by NIH grant #1U01HL112707-01. Additional GRADS funding is provided by NIH grant # 1U01HL112711-01.
category: Pulmonology
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Pitt Researchers Identify Agent That Can Block Fibrosis of Skin, Lungs

Posted by andrewsj3 on Wednesday, May 30th 2012     

PITTSBURGH, May 30 – Researchers at the University of Pittsburgh School of Medicine have identified an agent that in lab tests protected the skin and lungs from fibrosis, a process that can ultimately end in organ failure and even death because the damaged tissue becomes scarred and can no longer function properly. The findings were published today in Science Translational Medicine.

There are no effective therapies for life-threatening illnesses such as idiopathic pulmonary fibrosis and systemic sclerosis, which cause progressive organ scarring and failure, said senior author Carol A. Feghali-Bostwick, Ph.D., associate professor, Division of Pulmonary, Allergy and Critical Care Medicine, and co-Director of the Scleroderma Center, Pitt School of Medicine.

“It’s estimated that tissue fibrosis contributes to 45 percent of all deaths in developed countries because organ failure is the final common pathway for numerous diseases,” she said. “Identifying a way to stop this process from happening could have enormous impact on mortality and quality of life.”

The research team evaluated E4, a piece of protein or peptide derived from endostatin, a component of collagen known for its inhibition of new blood vessel growth. In lab tests, healthy human skin cells that were treated to become fibrotic remained normal when E4 was present. The skin and lungs of mice were protected from cell death and tissue scarring by a single injection of E4 administered five or eight days after they were given the cancer drug bleomycin, which is known to induce fibrosis. The peptide also could reverse scarring that had already occurred, the researchers found.

In a unique approach, the investigators also tested E4 in human skin maintained in the laboratory to confirm it would be effective in treating fibrosis in a human tissue. E4 blocked new and ongoing fibrosis in human skin.

The agent might work by stalling the cross-linking of collagen needed to form thick scars, Dr. Feghali-Bostwick said. While the body naturally produces endostatin, it appears that it cannot make sufficient amounts to counteract fibrosis development in some diseases.
“This endostatin peptide passes two important hurdles that suggest it is a promising candidate drug for development for patients with idiopathic pulmonary fibrosis and systemic sclerosis” said Mark T. Gladwin, M.D., chief, Division of Pulmonary, Allergy and Critical Care Medicine at UPMC and Pitt. “It reverses established disease in animal models and it reverses fibrosis in the human skin fibrosis model.”

In a case of serendipity, the researchers discovered E4 while exploring the process of fibrosis. Post-doctoral fellow and study co-author Yukie Yamaguchi, M.D., Ph.D., was conducting some experiments with proteins thought to facilitate the scarring process.
“Dr. Yamaguchi showed me the tests that showed endostatin wasn’t working to increase fibrosis, but in fact shut it down,” Dr. Feghali-Bostwick said. “It was the opposite of what we expected and I was very excited about our finding. As Louis Pasteur once said, ‘chance favors the prepared mind.’”

Other co-authors include Takahisa Takihara, M.D., Roger A. Chambers, B.S., and Kristen L. Veraldi, M.D., Ph.D., of the Division of Pulmonary, Allergy and Critical Care Medicine, the Department of Pathology, and the Scleroderma Center, Pitt School of Medicine; and Adriana T. Larregina, M.D., Ph.D., of the Departments of Dermatology and Immunology, Pitt School of Medicine, and the McGowan Institute for Regenerative Medicine.

The project was funded by National Institutes of Health grant AR050840.

category: Pulmonology, UPMC
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Surgical Pathology of Organ Transplantation Conference

Posted by UPMC Physician Resources on Thursday, March 15th 2012     

On May 4 and 5, 2012, join the lively discussion at the Surgical Pathology of Organ Transplantation Conference in Pittsburgh, Pa.

Organ procurement and the care of the transplanted patient occurs all over the world, in facilities large and small, academic and rural. The body of knowledge is growing exponentially. This event is designed for:

  •  pathologists
  • transplant surgeons
  • hepatologists
  • gastroenterologists
  • nephrologists
  • pulmonologists
  • cardiologists
  • oncologists
  • immunologists
  • infectious disease specialists
  •  residents, fellows and other health care professionals

You can view the conference brochure and agenda here.

The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The University of Pittsburgh designates this live activity for a maximum of 11.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Other health care professionals are awarded 1.1 continuing education units (CEU’s) which are equal to 11.25 contact hours.

category: Abdominal Transplant, Gastroenterology, HLTrans, Kidney, Pulmonology, Transplantation, UPMC
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