http://www.medscape.com/viewarticle/529690?src=mp

[The take-home message of this research is that "asthma exacerbations"
may really be chest infections.  That certainly has been my experience]

Telithromycin May Be Helpful in Adults With Acute Asthma Exacerbation
CME

News Author: Laurie Barclay, MD
CME Author: Hien T. Nghiem, MD

April 12, 2006 - Telithromycin improves the symptoms of and some
objective lung function tests in adults with acute exacerbations of
asthma, according to the results of a randomized trial reported in the
April 13 issue of The New England Journal of Medicine. However, the
editorialist agrees with the authors that it would be premature to
apply these findings clinically.

"Ketolides are a new class of antibiotics that are structurally related
to macrolides and have a bactericidal effect against Chlamydophila
pneumoniae and Mycoplasma pneumoniae," write Sebastian L. Johnston, MD,
PhD, from the National Heart and Lung Institute, Imperial College
London in England, and colleagues from The Telithromycin,
Chlamydophila, and Asthma Trial (TELICAST) Investigators. "Like
macrolides, the ketolide telithromycin (Ketek, Sanofi-Aventis) has
immunomodulatory effects both in vitro and in vivo. It is not known
whether treatment with a ketolide could improve treatment of an
exacerbation of asthma."

In this double-blind study, 278 adults with diagnosed asthma were
enrolled within 24 hours after an acute exacerbation of asthma
requiring short-term medical care, and they were randomized to receive
10 days of oral treatment with telithromycin (800 mg daily) or placebo
in addition to usual care. The main outcomes were a change from
baseline in symptoms recorded by patients on a diary card, scored on a
7-point scale, with 0 denoting no symptoms and 6 denoting severe
symptoms; and in peak expiratory flow measured in the morning at home.
Serologic analysis, polymerase chain reaction, and culture determined
the presence of C. pneumoniae or M. pneumoniae.

Of the 2 prespecified primary outcomes, only asthma symptoms showed a
significantly greater reduction in patients receiving telithromycin
than in patients assigned to placebo. Mean asthma symptom scores were
3.0 ± 1.4 at baseline and 1.7 ± 1.1 after telithromycin treatment
compared with 2.8 ± 1.3 at baseline and 2.0 ± 1.0 at the end of
treatment for the placebo group (mean decrease, 1.3 for telithromycin
and 1.0 for placebo; mean difference, -0.3; 95% confidence interval,
-0.5 to -0.1; P = .004).

There was no significant treatment effect observed on change in morning
peak expiratory flow, which was the other primary outcome measure.
Nausea was more common in the telithromycin group than in the placebo
group (P = .01). Although 61% of patients had evidence of infection
with C. pneumoniae and/or M. pneumoniae, bacteriologic status was not
correlated with the response to asthma treatment.

"This study provides evidence of the benefit of telithromycin in
patients with acute exacerbations of asthma; the mechanisms of benefit
remain unclear," the authors write. "Although this placebo-controlled
study provides evidence regarding the role of treatment with a specific
antibiotic in acute exacerbations of asthma, it does not provide
clinical guidance."

Study limitations include lack of accurate standardized laboratory
tests to diagnose infection with C. pneumoniae and M. pneumoniae;
poor-quality specimen collection at centers that do not specialize in
sputum sampling; and insufficient power to give reliable information
regarding extremely rare adverse events.

"Among adult patients with acute exacerbations of asthma, telithromycin
(at a daily dose of 800 mg for 10 days) led to an improvement in
symptoms and in lung-function tests performed in the clinic but not in
home-measured peak expiratory flow rates," the authors conclude.
"Further studies are required to confirm these results, to further
define patient populations who are most likely to benefit from the
treatment, and to elucidate the mechanisms of action."

Several authors have disclosed various financial relationships with
Sanofi-Aventis, Pfizer, GlaxoSmithKline, Bayer, Altana, Abbott, and/or
Berlex.

In an accompanying editorial, Frédéric F. Little, MD, from Boston
University School of Medicine in Mass, notes that the implications of
the TELICAST study are "provocative but not directive."

"Early studies assessing an antiinflammatory effect of macrolides in
the treatment of asthma have demonstrated a salutary effect on airway
hyperresponsiveness, as well as on certain inflammatory markers in
sputum," Dr Little writes. "It is tempting to speculate that the
results of the large, prospective, placebo-controlled TELICAST study
mirror these findings; it clearly establishes the foundation for
additional direct examination of this therapeutic opportunity in
asthma. It is time for further study, not for treatment."

Dr Little has disclosed no relevant financial relationships.

N Engl J Med. 2006;354:1589-1600, 1632-1634