See http://www.chestjournal.org/cgi/content/full/123/1/261?ck=nck

"It is well established that macrolide antibiotics are efficacious in
treating sinopulmonary infections in humans. However, a growing body of
experimental and clinical evidence indicates that they also express
distinct salutary effects that promote and sustain the reparative
process in the chronically inflamed upper and lower respiratory tract.
Unlike the anti-infective properties, these distinct effects are
manifested at lower doses, usually after a relatively prolonged period
(weeks) of treatment, and in the absence of an identifiable, viable
pathogen. Long-term, low-dose administration of macrolide antibiotics
has been used most commonly for sinusitis, diffuse panbronchiolitis,
asthma, bronchiectasis, and cystic fibrosis. It is associated with
down-regulation of nonspecific host inflammatory response to injury and
promotion of tissue repair. Although large-scale trials are lacking,
the prolonged use of these drugs has not been associated with emergence
of clinically significant bacterial resistance or immunosuppression.
Long-term, low-dose administration of 14- and 15-membered ring
macrolide antibiotics may represent an important adjunct in the
treatment of chronic inflammatory sinopulmonary diseases in humans."

"Asthma
Macrolide antibiotics, especially troleandomycin and erythromycin, have
been studied since the 1950s and have been shown to decrease
corticosteroid requirement in patients with corticosteroid-dependent
asthma. For instance, Spector et al reported a double-blind, crossover
trial comparing troleandomycin to placebo in 74
corticosteroid-dependent patients with severe asthma and chronic
bronchitis. Sixty-seven percent of patients had a marked improvement in
sputum production, pulmonary function measurements, need for
bronchodilators, and subjective evaluations. Much of this effect,
however, was attributed to troleandomycin-induced inhibition of
methylprednisolone and theophylline metabolism by the hepatic
cytochrome P450 complex.

In vitro studies have suggested that macrolide antibiotics have
beneficial anti-inflammatory and immunomodulatory effects in patients
with asthma who are independent of the corticosteroid metabolism.
Macrolide antibiotics inhibit lymphocyte proliferation in response to
phytohemagglutinin, decrease neutrophil accumulation through decrease
chemotactic activity, decreased mucus secretion, and decrease
contraction of isolated bronchial tissue.

Open-label studies with troleandomycin in methyprednisolone-dependent
patients with asthma (adults and children) have demonstrated greater
reduction in corticosteroid doses than would be predicted by hepatic
inhibition of corticosteroid metabolism.. Gotfried et al. showed a
significant improvement in pulmonary function test results and quality
of life measures in prednisone-dependent patients with asthma
administered a 6-week course of clarithromycin without any change in
prednisone requirements. In a small case series of patients
administered clarithromycin for 1 year, two of three
prednisone-dependent patients were able to discontinue prednisone
entirely.

Macrolide antibiotics are efficacious measures in asthmatic patients
without corticosteroid dependency by reducing airway hyperreactivity. A
10-week course of low-dose erythromycin was associated with a
significant decrease in bronchial hyperresponsiveness in asthmatic
patients tested by histamine challenge. Similar effects were observed
when hospitalized children were treated with roxithromycin. Tamaoki et
al showed that erythromycin, "roxithromycin, and clarithromycin
attenuated the contractile response of human isolated bronchial strips
to electrical field stimulation. They hypothesized that macrolide
antibiotics inhibit the cholinergic neuroeffector transmission in human
airway smooth muscle.

Another possible explanation for the efficacy of macrolide antibiotics
in patients with asthma is the role of chronic infectious diseases,
particularly Chlamydia pneumoniae. These infectious agents may underlie
acute asthma exacerbations and the initiation and maintenance of asthma
in previously asymptomatic patients. The anti-infective vs. tissue
reparatory effects of macrolide antibiotics in asthma will require
further controlled studies to unravel these pathways." Regards,
Richard Friedel