Chest
Recent Advances in Chest MedicineChronic Macrolide Therapy in Inflammatory Airways Diseases
Section snippets
Immunomodulatory Effects of Macrolide Antibiotics
Macrolide antibiotics belong to an expansive family of compounds that are characterized by the presence of a macrocyclic lactone ring.7 This family includes compounds that mainly have immunosuppressant activity (eg, FK 506 and rapamycin) or antifungal activity with antineoplastic properties (eg, bafilomycins).7 Macrolides exert their antimicrobial effect by binding to 50S ribosomes of both prokaryotic and eukaryotic organisms and inhibiting transpeptidation or translocation of nascent peptides.8
Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive disorder affecting one in 32,000 live white births in the United States. CF is caused by a defect in the cystic fibrosis transmembrane regulator.41 Alterations in epithelial cell ion transport as a result of defective CF transmembrane regulator lead to increased sputum viscosity, which causes stasis of secretions, recurrent respiratory infections, and chronic progressive bronchiectasis.42 Long-term effects of the bronchiectasis include impaired
Idiopathic Bronchiectasis
The effectiveness of long-term macrolides in DPB and CF led to interest in using these agents in patients with bronchiectasis not caused by CF (grouped as idiopathic bronchiectasis despite the fact that, in some instances, the cause of the bronchiectasis is known, such as ciliary dyskinesia, posttuberculous). There is ample evidence that, regardless of cause, bronchiectasis involves cyclical infection, inflammation, and mediator release.51, 56
Patients with idiopathic bronchiectasis have an
Asthma
Asthma is a chronic inflammatory disorder of the airways involving many cell types and numerous inflammatory mediators.65 The recurrent cough, wheeze, dyspnea, chest tightness, and episodic airflow limitation are caused by intermittent inflammation. Some suggest that chronic infection of the lower respiratory tract with Mycoplasma pneumoniae and/or Chlamydia pneumoniae may be an important contributor to the pathophysiology.66 The presence of chronic inflammation and possible chronic infection
COPD
COPD develops in susceptible smokers as a result of peripheral airway remodeling (ie, bronchiolitis) and parenchymal destruction (ie, emphysema).75, 76 Bronchial biopsies, BALF, and induced sputum all show increased numbers of neutrophils, macrophages, and CD8+ T cells.77, 78, 79 During the past decade numerous studies have confirmed the importance of chronic inflammation in both the airways and lung parenchyma.80, 81, 82 A variety of microbes stimulate the inflammatory process and precipitate
Posttransplant Bronchiolitis Obliterans Syndrome
Bronchiolitis obliterans syndrome (BOS) is a manifestation of chronic rejection (lung or bone marrow) and is responsible for the large majority of deaths following lung transplantation.89 Up to 50% of lung transplant recipients surviving at least 3 months will develop BOS.90 Given the substantial morbidity and mortality associated with BOS, combined with the limited effectiveness and common side effects of traditional antirejection therapies, there has been recent interest in assessing the
Other Airway Disorders
Organizing pneumonia is an inflammatory disease affecting the distal airways and alveoli. Stover and Mangino99 reported three patients with idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (now called cryptogenic organizing pneumonia) and three patients with radiation-related BOOP who responded to macrolide therapy. They recommended considering macrolide therapy for BOOP in patients with minimal symptoms and/or minimal physiologic impairment, as adjuvant therapy in patients
Conclusion
The introduction of chronic low-dose macrolide therapy for the treatment of DPB has altered the natural history of this disease and beneficial effects have been described in patients with many other inflammatory airways diseases. Numerous studies have described broad immunomodulatory effects of macrolides such that modulation of host-pathogen interactions, signaling pathways, cytokine responses, oxidative stress, and innate immunity likely contribute to these benefits. Although additional
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
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