Why Steroid Treatment for COPD Is Ineffective

Findings Offer Potential New Drug Target for COPD Therapy

 

Baltimore, Maryland, USA (October 17, 2011) – 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 corticosteroids 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 Medical Research Institute, the National Cancer Institute, the National Institute on Environmental Health and the Grace Anne Dorney fund for tobacco-related disease research.

 


 

Johns Hopkins Bloomberg School of Public Health, 17.10.2011 (tB).

MEDICAL NEWS

Fitness watches generate useful information, but increase patient anxiety
A new device provides added protection against COVID-19 during endoscopic…
81 million Americans lacking space or bathrooms to follow COVID…
Front-line physicians stressed and anxious at work and home
EULAR: High-Dose Glucocorticoids and IL-6 Receptor inhibition can reduce COVID-19…

SCHMERZ PAINCARE

Morbus Fabry mittels Datenanalysen aus dem PraxisRegister Schmerz aufspüren
Neandertaler besaßen niedrigere Schmerzschwelle
Deutscher Schmerz- und Palliativtag 2020 – ONLINE
Deutsche Gesellschaft für Schmerzmedizin fordert Anerkennung von Nicht-Psychologen in der…
DBfK: Besondere Rolle für Pflegeexpert/innen Schmerz – nicht nur in…

DIABETES

“Körperstolz”: Michael Krauser managt seinen Diabetes digital
Der richtige Sensor – von Anfang an
Diabetes mellitus: Ein Risikofaktor für frühe Darmkrebserkrankungen
Fastenmonat Ramadan: Alte und neue Herausforderung für chronisch Erkrankte während…
Sanofi setzt sich für die Bedürfnisse von Menschen mit Diabetes…

ERNÄHRUNG

Corona-Erkrankung: Fehl- und Mangelernährung sind unterschätze Risikofaktoren
Gesundheitliche Auswirkungen des Salzkonsums bleiben unklar: Weder der Nutzen noch…
Fast Food, Bio-Lebensmittel, Energydrinks: neue Daten zum Ernährungsverhalten in Deutschland
Neue Daten zur Ernährungssituation in deutschen Krankenhäusern und Pflegeheimen: Mangelernährung…
Baxter: Parenterale Ernährung von Patienten mit hohem Aminosäurenbedarf

ONKOLOGIE

Darolutamid bei Prostatakarzinom: Hinweis auf beträchtlichen Zusatznutzen
Multiples Myelom: Wissenschaftler überprüfen den Stellenwert der Blutstammzelltransplantation
Neues zur onkologischen Supportiv- und Misteltherapie und aktuelle Kongress-Highlights zum…
Finanzierung der ambulanten Krebsberatung weiterhin nicht gesichert
Lungenkrebsscreening mittels Low-Dose-CT

MULTIPLE SKLEROSE

Geschützt: Multiple Sklerose: Novartis’ Siponimod verzögert Krankheitsprogression und Hirnatrophie bei…
Neurofilamente als Diagnose- und Prognosemarker für Multiple Sklerose
Bedeutung der Langzeittherapie bei Multipler Sklerose – mehr Sicherheit und…
Bristol Myers Squibb erhält Zulassung der Europäischen Kommission für Ozanimod…
Einige MS-Medikamente könnten vor SARS-CoV-2/COVID-19 schützen

PARKINSON

Neue Studie zur tiefen Hirnstimulation bei Parkinson-Erkrankung als Meilenstein der…
Putzfimmel im Gehirn
Parkinson-Patienten in der Coronakrise: Versorgungssituation und ein neuer Ratgeber
Neuer Test: Frühzeitige Differenzialdiagose der Parkinson-Erkrankung
Gegen das Zittern: Parkinson- und essentiellen Tremor mit Ultraschall behandeln…