Researchers discover why steroid treatment for COPD is ineffective

October 18, 2011

(Medical Xpress) -- Chronic obstructive pulmonary disease (COPD) leads to persistent inflammation of the airways and is typically managed with corticosteroids, a class of anti-inflammatory medication. However, corticosteroids do not improve survival nor alter the progression of COPD and may reduce lung symptoms as little as 20 percent. A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health, found why corticosteroids do not work well for COPD patients and how additional treatment with sulforaphane—an ingredient of broccoli and other vegetables—can improve the effectiveness of corticosteroids. The study was published online October 17, 2011, in advance of print in the Journal of Clinical Investigation.

COPD is a major public health problem for both the developed and the developing world, and is most often caused by cigarette smoking or exposure to pollutants from combustion. Characterized by chronic bronchitis and emphysema, COPD is the third leading cause of death in the U.S. and affects 24 million Americans and 210 million people worldwide.

Histone deacetylase 2 (HDAC2) is critical component in a chain of reactions that enable to reduce inflammation. However, HDAC2 is substantially reduced in the lung tissue of individuals with COPD. In the study, Johns Hopkins researchers found that S-nitrosylation causes HDAC2 dysfunction and leads to corticosteroid insensitivity in the alveolar macrophages of the lungs of individuals with COPD. S-nitrosylation of HDAC2 occurs from exposure to cigarette smoke, a primary cause of COPD.

“This study provides the mechanism of exaggerated inflammation observed in COPD patients during exacerbations, which has been a barrier to developing effective therapy,” said Rajesh Thimmulappa, PhD co-author of the study and an assistant scientist in the Bloomberg School’s Department of Environmental Health Sciences.

Furthermore, the research team found that treatment with sulforaphane restored HDAC2 activity and corticosteroid sensitivity. Previous studies by the research team showed sulforaphane activates the Nrf2 pathway (nuclear factor erythroid 2–related factor 2) and it is being tested in clinical trial for patients with COPD.

“Restoring corticosteroid sensitivity in patients with COPD by targeting the Nrf2 pathway holds promise for effectively treating exacerbations,” said Shyam Biswal, PhD, senior author of the study and professor in the Bloomberg School’s Department of Environmental Health Sciences and Division of Pulmonary and Critical Care Medicine at the Johns Hopkins School of Medicine.

Authors of “Denitrosylation of HDAC2 by Targeting Nrf2 Restores Glucocorticosteriod Sensitivity in Macrophages from COPD Patient” are Deepti Malhotra, Rajesh Thimmulappa, Nicolas Mercado, Kazuhiro Ito, Ponvijay Kombairaju, Sarvesh Kumar, Jinfang Ma, David Feller-Kopman, Robert Wise, Peter Barnes and Shyam Biswal.

Funding for the research was provided by the National Institutes of Health, the National Heart, Lung and Blood Institute, the Flight Attendants Research Institute, the National Cancer Institute, the National Institute on and the Grace Anne Dorney fund for tobacco-related disease research.

Explore further: Compound in broccoli sprouts cleans out diseased lungs: Experimental treatment for COPD in development

Related Stories

Compound in broccoli sprouts cleans out diseased lungs: Experimental treatment for COPD in development

April 13, 2011
Researchers at the Johns Hopkins Bloomberg School of Public Health have developed a non-steroid based strategy for improving the lung's innate immune defense and decreasing inflammation that can be a problem for patients ...

LA BioMed investigators help spearhead study about novel approach to acute COPD illness

September 6, 2011
Richard Casaburi, Ph.D., M.D., principal investigator at Los Angeles Biomedical Research Institute, is co-author of a recent study that should help improve the condition for the millions of individuals who suffer from chronic ...

Computed tomography shows changes in lungs associated with COPD flare-ups

July 27, 2011
Using computed tomography (CT), researchers have identified two types of structural changes in the lungs of patients with chronic obstructive pulmonary disease (COPD) that are associated with frequent exacerbations, or episodes ...

Cell division abnormality contributes to inflammation in COPD

May 15, 2011
Changes in the ability of lung cells to divide may play a role in initiating or prolonging lung tissue inflammation, a hallmark of chronic obstructive pulmonary disease (COPD), according to a study conducted by researchers ...

Long-term inhaled corticosteroid use increases fracture risk in lung disease patients

June 23, 2011
Patients with chronic obstructive pulmonary disease (COPD) who use inhaled corticosteroids to improve breathing for more than six months have a 27 percent increased risk of bone fractures, new Johns Hopkins-led research suggests.

Recommended for you

Google searches can be used to track dengue in underdeveloped countries

July 20, 2017
An analytical tool that combines Google search data with government-provided clinical data can quickly and accurately track dengue fever in less-developed countries, according to new research published in PLOS Computational ...

MRSA emerged years before methicillin was even discovered

July 19, 2017
Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published in the open access journal Genome Biology. It was ...

New test distinguishes Zika from similar viral infections

July 18, 2017
A new test is the best-to-date in differentiating Zika virus infections from infections caused by similar viruses. The antibody-based assay, developed by researchers at UC Berkeley and Humabs BioMed, a private biotechnology ...

'Superbugs' study reveals complex picture of E. coli bloodstream infections

July 18, 2017
The first large-scale genetic study of Escherichia coli (E. coli) cultured from patients with bloodstream infections in England showed that drug resistant 'superbugs' are not always out-competing other strains. Research by ...

Ebola virus can persist in monkeys that survived disease, even after symptoms disappear

July 17, 2017
Ebola virus infection can be detected in rhesus monkeys that survive the disease and no longer show symptoms, according to research published by Army scientists in today's online edition of the journal Nature Microbiology. ...

Mountain gorillas have herpes virus similar to that found in humans

July 13, 2017
Scientists from the University of California, Davis, have detected a herpes virus in wild mountain gorillas that is very similar to the Epstein-Barr virus in humans, according to a study published today in the journal Scientific ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.