Chest
Immunomodulatory Activity and Effectiveness of Macrolides in Chronic Airway Disease
Section snippets
The Steroid-Sparing Effects of Macrolides
A number of studies91011121314 have shown an improvement in the clinical symptoms of corticosteroid-dependent patients with asthma and a reduction in corticosteroid dosage with concomitant TAO therapy. Pharmacokinetic studies1516 have suggested that the beneficial effects of TAO therapy may be due, in part, to the inhibition of steroid metabolism. TAO was shown to significantly prolong the serum half-life of methylprednisolone. However, in reported studies, some steroid-dependent patients were
The Effects of Macrolides on Mucus Secretion
Macrolide antibiotics also appear to be mucoregulatory, that is, they are able to decrease mucus hypersecretion in persons with airway disease without suppressing baseline physiologic secretion. In a double-blind, placebo-controlled, 8-week trial of 31 patients with chronic bronchitis, bronchiectasis, or DPB, low-dose clarithromycin (100 mg twice daily) profoundly decreased the expectorated sputum volume from 51 to 24 g per day (p < 0.001).19 Treatment with clarithromycin also increased the
The Effects of Macrolides on DPB
DPB is a chronic inflammatory pulmonary disease that is well-recognized in Japan and Korea, and is less commonly diagnosed in the West.242526 Although upper airway symptoms, including chronic sinusitis, usually begin in late childhood, DPB is usually diagnosed between the second and fifth decades of life, and is characterized by chronic, progressive, obstructive, and inflammatory sinobronchial disease. The clinical diagnostic criteria of DPB are given in Table 1.2 These criteria include airflow
Clinical Studies
Kudoh and colleagues27 were the first to demonstrate that low-dose erythromycin ameliorated the signs and symptoms of DPB. Therapy often will improve the appearance of chest radiographs and normalize pulmonary function. A large number of studies352728 have confirmed the effectiveness of long-term macrolide therapy for the treatment of DPB. These are summarized here.
In a retrospective analysis of 498 Japanese patients with DPB,2 a significant improvement in survival was associated with treatment
The Effects of Macrolides in CF
Based on the similarities between DPB and CF, macrolide antibiotics have now been studied as immunomodulatory medications for the treatment of CF.4142 In a pilot study,43 daily azithromycin was given for > 3 months (and up to a year) to 7 children aged 6 to 17 years with CF and P aeruginosa infection. During the study, no concomitant therapy with steroids, dornase alfa, or IV Ig was administered to these subjects. Excluding the first 2 months of treatment from their analysis, the authors
Conclusion
In nearly all reports, patients with DPB or CF who have received macrolide antibiotics have responded with dramatic improvements in pulmonary function. The treatment of DPB is the most striking example of the benefits of macrolides. Before the introduction of macrolide therapy, the 10-year survival rate was reported to be 12 to 50%,2 but since the introduction of macrolide therapy the 10-year survival rate is now > 90%. It is probable that patients with CF may realize similar benefits with
CME Questions
The American College of Chest Physicians designates this continuing medical education activity for 1 credit hour in category 1 of the Physician's Recognition Award of the American Medical Association. To obtain credit, please complete the question form at http://www.chestnet.org. Credit can be obtained ONLY through our online process.
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Diagnostic criteria for DPB include all of the following except:
- A.
FEV1 < 70% and Pao2 < 80 mm Hg
- B.
Elevated titers of cold hemagglutinin × ≥ 64
- C.
Bilateral
- A.
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Cited by (130)
Erythromycin inhibits cigarette smoke-induced inflammation through regulating the PPARγ/NF-κB signaling pathway in macrophages
2021, International ImmunopharmacologyPlastic bronchitis: A case report
2021, Revue Francaise d'AllergologieInula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium
2020, Journal of EthnopharmacologyCitation Excerpt :Thus clarithromycin possess anti-inflammatory and immunomodulatory actions extending beyond their antibacterial activity. ( Guillot et al., 2011; Rubin and Henke, 2004). Comparing activity of selected controls (budesonide and clarithromycin) with recent data regarding extracts and compounds used in traditional medicine it is worth to emphasize the promising competitiveness of phytotherapy.
Azithromycin suppresses Th1- and Th2-related chemokines IP-10/MDC in human monocytic cell line
2019, Journal of Microbiology, Immunology and InfectionMycoplasma pneumoniae
2017, Principles and Practice of Pediatric Infectious DiseasesEffects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial
2016, Respiratory MedicineCitation Excerpt :Modulation of inflammation in COPD might be one of the future keystones in the treatment of COPD. Although in our study we were not able to show effect of doxycycline on inflammation, other possible candidate to modulate inflammation in COPD are the group of macrolides, a group of broad spectrum antibiotics which has been shown to have significant immunomodulatory effects related to the macrolytic lactone ring [38]. Extensive research has been done with azithromycin showing a reduction in pro-inflammatory interleukins and TNF-α resulting in a decreased number of exacerbations and an increased time to next exacerbation [39,40].
Learning objectives:
- 1.
To be aware of the diagnostic criteria for DPB.
- 2.
To understand the clinical evidence for the efficacy of macrolides for the treatment of DPB and CF.
- 3.
To understand the potential immunomodulatory effects of macrolides for the treatment of chronic diseases of the airways.
- 4.
To understand the effects of macrolides on mucus secretion.
- 5.
To realize the immunomodulatory effects of macrolides are independent of their antimicrobial effects.
- 6.
To realize the clinical utility of these drugs for the treatment of chronic inflammatory conditions.
Neither Dr. Rubin, nor the department(s) with which he is affiliated, has received something of value (ie, any item, payment, or service valued in excess of $750.00) from a commercial or other party related directly or indirectly to the subject of this submission. He has received research grants and honoraria, and is a consultant for Abbott Laboratories. He has also received research grants from Zambon Pharmaceuticals. Neither Dr. Henke, nor the department(s) with which he is affiliated, has received something of value (ie, any item, payment, or service valued in excess of $750.00) from a commercial or other party related directly or indirectly to the subject of this submission. This article will be presenting information about immunomodulatory uses of macrolide antibiotics that is considered research and is not yet approved for any purpose.
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