Skip to Navigation
University of Pittsburgh
Print This Page Print this pages

September 27, 2012

Research Notes

Childhood viral infection likely means more allergic asthma in adulthood

Researchers in the Division of Pulmonary, Allergy and Critical Care Medicine in the School of Medicine have shown in an animal model that a common childhood virus disables the normal immune tolerance transferred from the mother to child through breast milk, leading to increased susceptibility for allergic asthma later in life. Their findings were reported in the online version of Nature Medicine.

Early in life, regulatory T cells, or Treg, play an important role in the establishment of immune tolerance, which can prevent the immune system from triggering an allergic reaction to antigens such as pollen and dust, explained senior authors Anuradha Ray and Prabir Ray, both faculty members in medicine and immunology.

“We know that recurrent infections by respiratory syncytial virus (RSV) that require hospitalization in early life increase the risk for asthma in adult life,” noted Anuradha Ray. “But, until now, it hasn’t been clear why this happens.”

Allergens and biologic molecules that suppress the immune system are transferred from mothers to infants via breast milk, which induces protective regulatory Tregs in the infants to help block the development, later in life, of allergic diseases such as asthma.

Lead author Nandini Krishnamoorthy, of the Division of Pulmonary, Allergy and Critical Care Medicine, said: “So we went from ‘bedside to bench’ to better understand the immunological impact of early, repeated RSV infection and to see if it affects Tregs.”

First, the research team fed newborn mice with breast milk from their mothers, who in turn had been exposed to the egg-white protein ovalbumin every other day for 10 days, to see if the babies would become tolerant to the protein.

The newborn mice were weaned after 21 days, then some were infected with RSV several times for the next three weeks to mimic human infection. In the sixth week, the young mice were challenged with ovalbumin.

Mice that had not been infected with RSV did not have an immune response to the ovalbumin, to which they had been exposed through their mothers’ milk, indicating they had developed tolerance for it.

Those that had been repeatedly infected with RSV, however, had increased immune cell infiltration in their airways and increased mucus production when challenged with the egg protein.

In another experiment, Treg cells were isolated from either the RSV-infected or uninfected mice and transferred into ovalbumin-exposed animals, which then were challenged with the protein. The cells from the uninfected mice, but not those from the infected ones, potently prevented airway inflammation and other markers of allergic reaction, the researchers found. They also noted that RSV promoted the production of regulatory proteins called cytokines, which foster inflammation, as well as triggered other changes in the cellular microenvironment altering the function of Treg cells.

Prabir Ray, who initiated the study, said: “So without the suppressive function of the Tregs, the mice developed inflammatory immune responses to the ovalbumin allergen and developed asthma-like symptoms. If the memory Tregs are crippled early in life, an important protective mechanism against allergens is lost, which increases susceptibility to asthma.”

Pitt members of the research team included Anupriya Khare, Timothy B. Oriss, Christina Morse, Manohar Yarlagadda, and Sally E. Wenzel, all of the Division of Pulmonary, Allergy and Critical Care Medicine, and Mahesh Raundhal, of the Division of Pulmonary, Allergy and Critical Care medicine and the Department of Immunology.

The project was funded by NIH.


Faculty member part of international research effort

Partha Roy, faculty member in bioengineering and pathology, is a member of the international research team funded through a grant from the National Health and Medical Research Council to the University of New England (UNE) in New South Wales, Australia.

The project, “Profilin: A Novel Target for Cancer Therapy,” will investigate a protein that is hypothesized to suppress tumor growth. The team includes researchers from the United States, Denmark and Australia.

Roy will support the UNE project’s research team as an expert in assessing phenotype and oncogenic signaling in tumor cells after perturbation of profilin, an important actin-binding protein.


Study seeks acceptance by peers of young brain-tumor survivors

Robert Noll, a professor of pediatrics, psychiatry and psychology in the School of Medicine and a pediatric psychologist at Children’s Hospital, has been awarded a grant of $98,917 from the St. Baldrick’s Foundation, a nonprofit organization that raises money for childhood cancer research.

Noll will conduct a research-backed, school-based project to support brain tumor survivors’ social involvement by training classmates to be more inclusive of others viewed as “different.”

Children surviving brain tumors often have physical problems (jerky movements, slurred speech, vision, hearing, etc.) and cognitive delays caused by their disease or treatment.

These brain tumor survivors frequently are described by peers as “not well liked,” “having few friends” and “isolated,” which puts them at risk for being bullied, dropping out of school and becoming anxious or depressed.

“While the majority of children with cancer during therapy and afterwards seem to fit in quite well with peers, a different picture emerged for brain tumor survivors,” Noll said.

Noll leads several National Institutes of Health (NIH)-funded investigations focused on understanding the impact of chronic illness on children and their families.

His areas of expertise include quality of life for children with chronic illness; clinical trials of cognitive behavioral therapy to reduce distress after the diagnosis of cancer in a child, and bioethical issues in pediatric oncology related to informed consent.


Grants fund projects for wounded vets, persons with disabilities

The National Science Foundation awarded a $472,794 grant to Rory Cooper and Mary Goldberg of the Human Engineering Research Laboratories and the School of Health and Rehabilitation Sciences (SHRS) to study pathways for military veterans with disabilities who are transitioning into education.

The project aims to create a model for such veterans and people with disabilities to succeed in science, technology, education and math (STEM) programs.

This marks the second education-related award Cooper and his team have received in the past two months: in July the researchers secured a five-year, $3 million grant to support interdisciplinary research training in graduate-level engineering and rehabilitation. That grant entails traineeships to design innovative rehabilitation devices, systems and techniques that not only help people with disabilities participate in society but also utilize veterans and persons with disabilities as researchers and scientists.

Cooper is the FISA & Paralyzed Veterans of America (PVA) Chair and Distinguished Professor of the SHRS Department of Rehabilitation Science and Technology and a faculty member in bioengineering, mechanical engineering, physical medicine and rehabilitation and orthopaedic surgery.

He also is the co-director of the NSF Quality of Life Technology Engineering Research Center, a joint effort of Pitt and Carnegie Mellon University and Veterans Health Administration Senior Research Career Scientist of the VA Rehabilitation Research and Development Center of Excellence.


Antibiotic use varies

Doctors treating older patients in southern states are more likely to prescribe antibiotics than in any other region of the United States, according to a Pitt study that could guide and target policy efforts to prevent antibiotic overuse.

In an examination of antibiotic use among people age 65 and older using national Medicare Part D data from 2007-09,  Graduate School of Public Health faculty member Yuting Zhang and her colleagues found substantial geographic and seasonal variation in antibiotic use. The variation persisted after adjusting for regional differences in population demographics, insurance status and clinical characteristics, such as health status measured by risk scores or an extended nursing home stay.

The findings were published in the online issue of the Archives of Internal Medicine, a JAMA Network journal.

“Overuse of antibiotics is common and the consequences of overuse are substantial,” said Zhang, director of the pharmaceutical economics research group in the Department of Health Policy and Management, and lead author of the study. “Not only can it lead to unnecessary spending for prescription drugs, it can also increase antimicrobial resistance.

“Unnecessary drug prescribing in the elderly can be especially dangerous because of older patients’ increased susceptibility to side effects and allergic reactions,” Zhang added.

In the South, an average of 21.4 percent of patients seen in outpatient settings filled an antibiotic prescription in 2007-09. The rate was lowest in the West, at 17.4 percent of patients. In the Midwest, 19.2 percent of patients filled an antibiotic prescription, while 18.2 percent of patients in the Northeast did.

Regional variation in antibiotic prescribing did not seem to be explained by regional differences in the prevalence of major infections. For example, the South had the highest rates of non-specific upper respiratory infections, for which antibiotics typically are not recommended because these types of infections are viral.

This information could be used to create and refine programs that seek to reduce unnecessary antibiotic use, Zhang said. The low rates of antibiotic use in the West could be used as an example of an attainable goal for other regions.

The season also influenced antibiotic use rates, which were highest in January-March, at 20.9 percent, and lowest in July-September, at 16.9 percent. The rate was 18.5 percent in April-June, and 19.8 percent in October-December.

The Medicare population used more antibiotics, at 1.1 prescriptions per year, compared to previous findings of 0.88 prescriptions per year in children and adults younger than 65.

“Older adults often have multiple disorders or diseases, making them more susceptible to complications from untreated infections,” said Zhang. “So there is an incentive for physicians to treat older patients more aggressively with antibiotics. However, older patients might be subject to more severe adverse outcomes of antibiotic use and bacterial resistance is a societal concern. Thus, physicians should be extra careful to ensure not to prescribe unnecessary antibiotics to older patients.”

Cameron M. Kaplan of the Department of Health Policy and Management was a co-author on the study.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

We welcome submissions from all areas of the University. Submit information via email to:, by fax to 412/624-4579 or by campus mail to 308 Bellefield Hall.

For submission guidelines, visit

Leave a Reply