Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma

Abstract

A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma.Adult asthma patients undergoing treatment with budesonide 400 mg b.i.d. and salbutamol 200 mg p.r.n. less than twice weekly were studied. Arm A (16 males/six females, aged 48 ¡ 16 yrs) received clarithromycin 250 mg b.i.d. for 8 weeks, arm B (eight males/12 females, aged 42¡12 yrs) clarithromycin 250 mg t.i.d. and arm C (six males/15 females, aged 41¡16 yrs) placebo dextrose tablets. Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20).Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively. Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients.It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma. Asthma is characterised by bronchial hyperresponsiveness (BHR) to nonspecific stimuli such as histamine, methacholine, cold air and exercise. BHR is related to airway inflammation and the degree of BHR indirectly reflects the severity of the disease [1]. Systemic corticosteroids administered on a long-term basis reduce BHR, but their use has been associated with significant side-effects. Modern asthma research is orientated towards the use of inhaled corticosteroids, which also decrease BHR, or alternative drug therapies possessing less toxic immunosuppressive, immunomodulating and antiinflammatory qualities.Macrolides such as troleandomycin and erythromycin have been shown to be effective in the treatment of asthma [2,3]. Their action in the steroid-dependent asthmatic patient is mediated at least in part by decreased corticosteroid metabolism. For example, troleandomycin and clarithromycin decrease methylprednisolone clearance and increase plasma methylprednisolone levels [4,5]. However, clarithromycin does not have a significant effect on prednisolone elimination [5]. Erythromycin and especially the newer macrolides (e.g. roxithromycin, clarithromycin and azithromycin) exert specific anti-inflammatory effects, including inhibition of generation of reactive oxygen species by polymorphonuclear leucocytes [6,7]. In addition, macrolide antibiotics may improve lung function due to their activity against Mycoplasma pneumoniae and Chlamydia pneumoniae, which are involved in asthma exacerbations [8][9][10].As a result of the actions described above, macrolides probably reduce the severity of BHR in adults and children with asthma. Most published data on reduction of BHR refer to erythromycin, roxithromycin or azithromycin [11][12][13]. There are very few data on the ...

Long-term macrolide treatment for chronic respiratory disease

“…The possibility of chronic infection with organisms that are sensitive to macrolides provides a strong rationale for their use in asthma, although macrolides may also function as steroid-sparing or antiinflammatory agents [51,52]. Early studies have reported conflicting results [53][54][55][56][57].…”

Long-term macrolide therapy in chronic inflammatory airway diseases

“…Patients taking oral or inhaled corticosteroid were excluded. The second study examined asthmatics taking 800 mg budesonide daily; serum-free cortisol levels showed no change from baseline levels after treatment with clarithromycin, suggesting that altered steroid metabolism was not the effect mechanism [47]. Evidence for reduced bronchial hyperresponsiveness has also been demonstrated after treatment with erythromycin, roxithromycin and azithromycin [55][56][57].…”

“…Two studies have shown significant reductions in bronchial hyperresponsiveness in patients with asthma after 8 weeks' treatment with clarithromycin; neither showed any significant change in FEV1 [47,50]. The first study examined 17 patients with allergy-induced asthma and demonstrated a significant reduction in blood and sputum eosinophil counts, suggesting a possible anti-inflammatory role for clarithromycin [50].…”

Treatment with anti‐inflammatory drugs in community‐acquired pneumonia

“…Although it is known that macrolides possess such properties, it is difficult to independently assess the immunomodulatory and antimicrobial effects. Administration of macrolides has been shown to be beneficial in patients with chronic pulmonary inflammatory diseases, including diffuse panbronchiolitis [48], cystic fibrosis [49] and asthma [50]. Whether macrolides also exert favourable immunomodulatory effects during acute pulmonary infection is less clear.…”