Advances in Combination Therapy for Asthma and COPD by Jan Lotvall

Author:Jan Lotvall
Language: eng
Format: epub
ISBN: 9781119978466
Publisher: Wiley
Published: 2011-10-04T04:00:00+00:00

8.10 Infections in asthma and COPD

Some small uncontrolled serological studies suggest that Chlamydia pneumoniae infection may amplify the inflammation that occurs in severe persistent asthma and that asthma will subsequently improve with antibiotic therapy.212–214 However, that is not the case in all asthmatics.215–218 Similar reports have also associated the onset of persistent asthma with Mycoplasma pneumoniae infection.215,219 In addition to treating the infection present, macrolide antibiotics have been show to have some direct anti-inflammatory effects. For example, clarithromycin treatment in asthmatic patients could reduce the oedematous area as identified by α2-macroglobulin staining, which may lead to airway tissue shrinkage and cause an artificial increase in the number of blood vessels.220

Respiratory viral and/or bacterial infections are a major cause of asthma exacerbations.1 Therefore, antiviral treatments may be beneficial for asthma exacerbations. Telithromycin, a macrolide antibiotic, caused a small but significant reduction in asthma symptoms without changes in lung function compared to placebo when administered to patients with acute exacerbations of asthma.221 In addition, clarithromycin can reduce CXCL8 levels and sputum neutrophilia and improve asthma quality of life in patients with refractory non-eosinophilic asthma.222 It is unclear whether these macrolide antibiotics act by directly inhibiting infections or by inhibiting neutrophil-based inflammation. Despite the increasing evidence that persistent infection with Chlamydia pneumoniae is linked to chronic diseases including atherosclerosis and myocardial infarction, the role of Chlamydia pneumoniae infection in the onset of COPD remains controversial. The majority (54–77%) of patients with COPD show serological evidence of past infection with Chlamydia pneumoniae,223–225 but the incidence is similar to that seen in age-matched healthy subjects.223,226,227 There is some evidence that persistent Chlamydia pneumoniae infection may amplify the inflammation that occurs in COPD,228,229 but a prospective serological study suggests that chronic Chlamydia pneumoniae infection is not a major risk factor for progressive airflow obstruction.230 Clearly, further studies are necessary to determine whether chronic infection with Chlamydia pneumoniae is important in the pathogenesis of COPD or whether the organism is simply a ‘bystander’.

Therapeutic interventions aimed at treating viral or bacterial infections by inhibition of Toll-like receptors (TLRs) are also under investigation, although evidence in animal models is inconclusive.231

Furthermore, rhinovirus infection can reduce glucocortico receptor (GR) nuclear translocation and corticosteroid function,232 and, conversely, inhibition of the GR-associated heat-shock protein-90 (hsp-90) by geldanomycin or its analogues can attenuate rhinovirus replication without the formation of drug-resistant strains,233 implying mutual antagonism between viral infection and corticosteroids.

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