Thursday, December 20, 2007

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation

doi:10.1016/j.jaci.2007.09.017    How to Cite or Link Using DOI (Opens New Window)  
Copyright © 2007 American Academy of Allergy, Asthma & Immunology Published by Mosby, Inc.

Reviews and feature articles

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation

Leif Bjermer MDCorresponding Author Contact Information, a, E-mail The Corresponding Author
aDepartment of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden
Received 27 December 2006;  revised 13 September 2007;  accepted 14 September 2007.  Available online 9 December 2007.

Inflammation is a key pathology in asthma. In the central airways local inflammation leads to irreversible remodeling and airway dysfunction. Complex inflammatory changes also occur in the nose, sinuses, and small airways. In particular, rhinitis and asthma are linked by a common pathogenic process with common inflammatory cells, mediators, and cytokines. Cross-communication between the airways and bone marrow through inflammatory mediators in the circulation leads to systemic propagation of airway inflammation. Treatment of asthma has traditionally focused on relieving bronchospasm with β2-agonists, which do not affect inflammation. Treatment of eosinophilic inflammation in the central airways with inhaled corticosteroids reduces local inflammation and improves pulmonary function but does not improve the systemic manifestations of asthma. If asthma is a systemic disease, the underlying systemic pathology should be targeted by identifying common disease mediators, mechanisms, or both that are triggered only during active disease. Of currently available therapies, leukotriene receptor antagonists block the action of cysteinyl leukotrienes and thus improve both asthma and rhinitis and other conditions systemically linked with asthma. Other potential treatments include receptor-blocking molecules and synthesis inhibitors related to eicosanoid inflammation. Treatment of asthma as a systemic disease requires clinical trials that evaluate the effects of new treatments on both lung function and the wider systemic pathology.


Key words: Anti-inflammatory effects; anti-IgE; asthma; atopic dermatitis; β2-agonist; eosinophilic inflammation; inflammatory mediators; inhaled corticosteroids; leukotriene receptor antagonist; paradigm shift; small airways; systemic inflammation; rhinitis

Abbreviations: Cys-LT1, Cysteinyl leukotriene receptor; ICS, Inhaled corticosteroid; LTRA, Leukotriene receptor antagonist


Disclosure of potential conflict of interest: L. Bjermer has received consultant honorarium from Niigard Pharma.
Corresponding Author Contact InformationReprint requests: Leif Bjermer, MD, Respiratory Medicine & Allergology, University Hospital, Lund 22185, Sweden.



Journal of Allergy and Clinical Immunology
Volume 120, Issue 6, December 2007, Pages 1269-1275
 

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