Asthma diagnosis and treatment
Macrolide antibiotics and asthma treatment

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Treatment for acute asthma exacerbations is a major need not adequately met by current therapies. Although virus infections are the major cause of acute exacerbations, other factors can increase the risk/severity of exacerbations. Increasing evidence suggests atypical bacterial infections contribute to exacerbation severity, as well as stable asthma, particularly severe asthma. Macrolide antibiotics and the new ketolide antibiotic telithromycin are active against atypical bacteria and also have anti-inflammatory activity. A recent study has shown telithromycin to be effective in the treatment of acute exacerbations of asthma, although the mechanism or mechanisms of action were not determined. Controlled studies report small improvements in lung function with macrolide treatment of stable asthma. Further studies are urgently required to assess the role of such therapies in acute exacerbations and in severe stable asthma, in which the risk/benefit ratios are likely to be most in favor of therapy demonstrated to be effective.

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Evidence for increased susceptibility to infections in patients with asthma

Asthmatic individuals have increased susceptibility to rhinovirus infection in that they have more severe and more prolonged lower respiratory tract symptoms and greater reductions in lung function when infected than do healthy subjects.4 The mechanisms of this increased susceptibility are poorly understood, but one mechanism likely to play a significant role has been recently discovered. Primary bronchial epithelial cells from asthmatic subjects infected with rhinovirus in vitro were found to

Role of C pneumoniae and M pneumoniae in stable asthma

We have recently demonstrated that atopic asthmatic adults have increased frequencies of detection of C pneumoniae than do healthy subjects. In this study 74 spouse pairs consisting of an atopic asthmatic volunteer and a nonatopic healthy volunteer underwent regular nasal aspirate sampling, independent of symptoms, every 2 weeks during a 3-month period. The spouse pair design was undertaken to match for exposure to infectious agents as closely as possible. In atopic asthmatic patients 23 (6.4%)

Role of C pneumoniae and M pneumoniae in asthma exacerbations

Viral infections have been established by a number of studies to be associated with 80% to 85% of asthma exacerbations in children and around 70% to 75% of asthma exacerbations in adults. Virus infections have also been shown to interact with both allergen exposure9 and air pollution10 in increasing the risk of exacerbation and the severity of lower respiratory tract symptoms, respectively, indicating that viruses frequently interact with other cofactors in increasing the risk/severity of

Macrolide and ketolide antibacterial agents

A number of different antibacterial agents have activity against C pneumoniae and M pneumoniae, including tetracyclines, macrolides (azithromycin, clarithromycin, erythromycin, and roxithromycin), and the ketolide telithromycin. Newer macrolides accumulate intracellularly and have good activity against atypical organisms.

The ketolides are a new class of antibacterial agents related to macrolides but that have structural modifications that confer a broader range of antibacterial activity.

Role of macrolides in patients with stable asthma

A Cochrane review of macrolide treatment studies in patients with chronic stable asthma identified only 5 studies (including 357 patients) that met the required criteria (randomized placebo-controlled study of macrolide therapy of >4 weeks' duration).14 There was an overall positive effect on symptoms with macrolide therapy. However, these were not sufficiently consistent to permit recommendations regarding clinical care.

Furthermore, only one study investigated atypical bacterial infection,

Role of macrolides in asthma exacerbations

Current treatment guidelines indicate that antibiotics should not be given routinely in the treatment of acute exacerbations of asthma because evidence indicates viral infections to be the major cause. However, the evidence discussed above for a possible contributing role for atypical bacterial infection in acute exacerbations has prompted a recent study investigating the role of an antibiotic active against these infections.

The Telithromycin, Chlamydophila, and Asthma (TELICAST) study is a

Conclusions and future studies required

There is increasing evidence that infection with atypical bacteria plays a role in the pathogenesis of stable asthma, as well as in asthma exacerbations. The TELICAST study provides evidence of a therapeutic benefit with treatment with a ketolide antibiotic in asthma exacerbations. These finding are provocative and require confirmation but, if confirmed, could open new avenues for the treatment of asthma phenotypes not adequately served by currently available therapies. It will also be

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Disclosure of potential conflict of interest: S. Johnston has consulting arrangements with Sanofi-Aventis, Pfizer, and GlaxoSmithKline.

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Copyright © 2006 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.