Researchers discover why steroid treatment for COPD is ineffective

(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.

Provided by Johns Hopkins Bloomberg School of Public Health

5 /5 (1 vote)

Related Stories

COPD? Eat your veggies

Sep 12, 2008

You know it's good for you in other ways, but could eating your broccoli also help patients with chronic lung disease? It just might.

Recommended for you

Obama addresses West Africans on facts about Ebola

3 minutes ago

President Barack Obama urged West Africans on Tuesday to wear gloves and masks when caring for Ebola patients or burying anyone who died of the disease. He also discouraged the traditional burial practice ...

Gluten-free diet benefits asymptomatic EmA+ adults

6 minutes ago

(HealthDay)—Asymptomatic individuals with endomysial antibodies (EmA) benefit from a gluten-free diet (GFD), according to a study published in the September issue of Gastroenterology.

Another US health worker infected with Ebola

24 minutes ago

A third American health worker has tested positive for the Ebola virus while working with patients in West Africa, the Christian missionary group SIM said Tuesday.

UN implores all countries to help on Ebola

2 hours ago

The international group Doctor Without Borders warned Tuesday that the world is 'losing the battle' against Ebola, while U.N. officials implored all countries to quickly step up their response by contributing health experts ...

Travel restrictions could worsen Ebola crisis: experts

6 hours ago

Travel restrictions could worsen West Africa's Ebola epidemic, limiting medical and food supplies and keeping out much-needed doctors, virologists said Tuesday as the disease continued its deadly spread.

User comments