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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Understanding and Effectively Managing Allergic Respiratory Disease

To provide physicians with the most recent information regarding the treatment of asthma and allergic rhinitis as one condition.

This program is designed for allergists, otolaryngologists, pulmonary specialists, and primary care physicians. No prerequisites required.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Identify therapeutic areas in allergic disease in which new information is emerging and discuss the impact that this information may have on current management strategies.
  • Discuss the reasoning for treating asthma and allergic rhinitis as one condition.
  • Evaluate the reasons for the expanding role of antihistamines in the treatment of allergic diseases.
  • Evaluate the safety issues associated with newer antihistamines.

The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.

Release date: July 15, 2004. Expiration date: July 15, 2006.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Aventis Pharmaceuticals.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:


Alkis G. Togias, MD
Associate Professor of Medicine
Division of Clinical Immunology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Togias reports receiving grants/research support from Genentech and Merck & Co, Inc; serving as a consultant to AstraZeneca LP, Baxter Healthcare Organization, Genentech, GlaxoSmithKline, Merck & Co, Inc, and Novartis Corporation; and receiving honoraria from Genentech, Merck & Co, Inc, Novartis Corporation, Pfizer Inc, and UCB Pharma.


Michael S. Blaiss, MD
Associate Professor of Pediatrics and Medicine
Director of Clinical Immunology Training Program
University of Tennessee
Memphis, Tennessee
Dr Blaiss reports serving as a consultant to and receiving honoraria from Aventis Pharmaceuticals, Genentech, GlaxoSmithKline, Merck & Co, Inc, and Novartis Corporation; and receiving honoraria from AstraZeneca LP.

Erwin W. Gelfand, MD
Department of Pediatrics
National Jewish Medical and Research Center
Denver, Colorado
Dr Gelfand reports receiving grants/ research support from and serving as a consultant to Aventis Pharmaceuticals.

Ian Hindmarch, PhD
Professor of Human Psychopharmacology
Head, HPRU Medical Research Centre
University of Surrey
Guildford, Surrey, United Kingdom
Prof Hindmarch reports receiving grants/ research support from Aventis Pharmaceuticals, Bools, GlaxoSmithKline, Lichtwer, Lundberk, Mod (UK), Pfizer Inc, Pharmacia Corporation, Sanofi-Synthelabo, Servier, UCB Pharma, and Wyeth Pharmaceuticals.

Peter H. Howarth, DM, FRCP
Reader in Medicine
Honorary Consultant Physician
Respiratory Cell and Molecular Biology
Southampton General Hospital
Southampton, United Kingdom
Prof Howarth reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Gianni Marone, MD
Professor of Medicine
Department of Clinical Immunology and Allergy 
University of Naples Federico II
Naples, Italy
Prof Marone reports having no significant financial or advisory relationships with corporate organizations related to this activity.

In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Togias—ciclesonide, formoterol/budesonide combination

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

New Ideas On The Role Of Antihistamines In Allergic Airway Disease
Erwin W. Gelfand, MD,* and Michael S. Blaiss, MD†

Asymposium held at the 2003 World Allergy Congress, September 2003, explored the latest research taking place in the field of the therapeutic role of  antihistamines and their potential application in a broader range of allergic disorders, such as asthma. The proceedings from this symposium in this issue of Advanced Studies in Medicine were developed by internationally renowned speakers to highlight new concepts and clinical evidence that should furnish the physician with more information upon which to base the treatment of allergic rhinitis, and bring to a wider audience the ongoing research that may lead to future therapies.

Histamine plays a key role in the early phase of the allergic response, particularly through activation of H1-receptors. However, histamine also plays a significant role in the late-phase allergic response: histamine receptors—particularly H1-receptors on inflammatory cells—lead to increased expression of adhesion molecules as well as increased production of proinflammatory cytokines from endothelial cells, peripheral blood mononuclear cells, macrophages, and dendritic cells. If, as has been suggested, H1-antihistamines are inverse-receptor agonists, rather than antagonists, this may offer one explanation for the anti-inflammatory effects shown with some of these agents.

Data presented at the symposium suggest that basophil and mast-cell activation and the release of mediators, such as histamine, trigger early stimulation of lung macrophages, the predominant cell in bronchoalveolar lavage fluid and lung parenchyma. Lung macrophages are a major source of lysosomal enzymes and several cytokines that play a central role in tissue damage and remodeling, suggesting that there is a close and dynamic interaction between the processes mediating allergic inflammation and those resulting in tissue remodeling. As tissue remodeling may initiate early on in the sequence of events underlying allergic disorders, the implication exists that antihistamine treatment, as a means of preventing tissue remodeling in allergic disease, should also begin at an early stage.

The focus of the symposium moved from the laboratory to the clinic, with an overview of the use of antihistamines in children with allergic rhinitis. As with adults, the prevalence of allergic rhinitis in children is high and increasing. Furthermore, the impact on a child's quality of life (QOL) can be profound: children with allergic rhinitis exhibit impaired learning performance, are likely to miss school, and find it more difficult to integrate with peers. In addition, the impact of their symptoms can be a cause of family dysfunction. Any treatment must be effective at controlling symptoms, but must also be safe, without negatively affecting QOL. Sedating first-generation antihistamines should not, therefore, be the first choice of treatment in this population. Trials of newer-generation antihistamines have shown cetirizine, loratadine, and fexofenadine to be safe and effective.

The impact on QOL can be viewed as a manifestation of drug safety and effectiveness. Administration of antihistamines, which cross the blood-brain barrier and bind to H1-receptors in the brain, can produce sedation and impair cognitive function. In turn, this can put patients at risk when performing daily tasks, such as driving, and reduce QOL. There is a need for rigorous assessments and pharmacologic evidence that do not rely on subjective measurements to determine the intrinsic impairment caused by antihistamines. The penetration of an agent into the central nervous system can be measured objectively using psychometric tests, positron emission tomography, and lipophilicity. The older-generation antihistamines are clearly impairing, but the newer-generation agents do not represent a homogeneous group. Loratadine and cetirizine both penetrate the blood-brain barrier and can cause sedation at higher doses.

The concept of the "therapeutic window" is a succinct means of comparing the dosing properties of antihistamines. The therapeutic window of an H1-receptor antagonist is the efficacy-to-safety ratio of the agent; its range represents doses that are effective without causing undesirable side effects. A broad therapeutic window is advantageous for an H1-antihistamine, not only in terms of limiting the impact of potential drugÐdrug interactions and overall adverse-event profile, but also for use in patients who may increase their antihistamine dose in order to obtain further symptom relief.

*Chairman, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado.

†Associate Professor of Pediatrics and Medicine, Director of Clinical Immunology Training Program, University of Tennessee, Memphis.

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