Case report

Diffuse panbronchiolitis: efficacy of low-dose erythromycin

Roxithromycin is effective in the treatment of intracellular organisms, including chlamydia and mycoplasma, and exhibits anti-inflammatory and immunomodulatory effects on respiratory diseases. To explore the potential therapeutic benefit of roxithromycin in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), this study compared the effect of roxithromycin with ciprofloxacin and aceclofenac. A total of 75 patients with CP/CPPS were randomized to three groups in open-label: group 1, ciprofloxacin; group 2, aceclofenac; and group 3, roxithromycin. The patients were treated for 4 weeks and were subsequently followed for 12 weeks. Changes from baseline in the total and domain scores of the NIH Chronic Prostatitis Symptom Index (NIH-CPSI) were evaluated. The NIH-CPSI score decreased in the roxithromycin, ciprofloxacin, and aceclofenac groups to a similar degree. The NIH-CPSI initial and 12-week total scores were 20.3 and 10.0, respectively, in group 1; 23.6 and 14.3, respectively, in group 2; and 21.1 and 9.8, respectively, in group 3. The three treatment arms did not differ significantly with respect to the efficiency of treatment (p > 0.05). Compared to patients in groups 1 and 2, group 3 patients with Category IIIb disease exhibited favorable results upon follow-up 12 weeks after treatment. The International Prostate Symptom Score (IPSS), uroflowmetry, and post-void residual volume were equivalent between the groups. Roxithromycin exhibits similar or favorable effects on the improvement of CP/CPPS compared to ciprofloxacin and aceclofenac. Roxithromycin could be used as a new therapeutic agent for CP/CPPS. Further study of the immunomodulatory action of roxithromycin in CP/CPPS is required. (ClinicalTrials.gov Identifier: NCT01843946).

Interest in azithromycin in the management of patients with cystic fibrosis has grown over the last decade. Uniquely this drug has both antibacterial and immune modulating effects which appear to be the reason for its clinical benefit as proven in several well designed clinical studies. In this review we discuss the proposed mechanisms of action of azithromycin and review the evidence for its clinical effectiveness and safety in cystic fibrosis.

Diffuse panbronchiolitis (DPB) is a life-threatening airway disease in which neutrophils persistently and massively emigrating to the airways cause progressive and irreversible tissue damage. However, the pathogenesis of the airway inflammation remains unclear. The failure of non-inflammatory removal of emigrating neutrophils due to delayed apoptosis has been proposed as a mechanism by which the neutrophilic inflammation persists. Therefore, we aimed to investigate whether an activity that delays neutrophil apoptosis is present at the inflamed sites in DPB. Neutrophils isolated from normal volunteers were cultured with sputum extracts of patients with DPB, and viability and apoptosis of neutrophil was evaluated for the culture period. Neutrophils cultured with sputum extracts for 2 and 3 days showed significantly enhanced survival compared to those with medium alone. The neutrophil survival-enhancing activity in sputum extracts was heat-labile and partially, but significantly, neutralized with anti-human GM-CSF, but not with anti-human G-CSF antibody. The enhancement of neutrophil survival was associated with an inhibition of apoptosis demonstrated by cytology, TUNEL assay and DNA fragmentation analysis. These results suggest that neutrophil apoptosis is prevented by survival-enhancing factors including GM-CSF in the airways of DPB, leading to neutrophil death by necrosis that causes further recruitment and activation of neutrophils.

Diffuse panbronchiolitis (DPB) is a chronic progressive disease of the respiratory bronchioles, and has been improved by low-dose, long-term erythromycin (EMC) treatment. The therapeutic benefits may be derived from its anti-inflammatory and immunomodulatory properties rather than antimicrobial effect. However, there are few studies about the mechanism of immunomodulation by EMC treatment for patient with DPB. In this study, we quantified the changes of Th1 and Th2 cytokines in the bronchoalveolar lavage (BAL) fluid from patients with DPB after long term treatment with EMC. After the EMC treatment, a significant reduction in the number of lymphocytes was observed, and the CD4/CD8 ratio was elevated as well. The IL-2 and IFN-γ levels in the BAL fluid were significantly decreased and the IL-4, IL-5, and IL-13 levels were significantly increased after EMC treatment. Our results suggest that the therapeutic benefits of long-term EMC treatment may be partially due to the immune system’s shift from Th1 to Th2 cytokine production.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (se) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P<0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3–6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.