ABSTRACT
Long-term therapy with the macrolide antibiotic erythromycin was shown to alter the clinical course of diffuse panbronchiolitis in the late 1980s. Since that time, macrolides have been found to have a large number of antiinflammatory properties in addition to being antimicrobials. These observations provided the rationale for many studies performed over the last decade to assess the usefulness of macrolides in other inflammatory airways diseases, such as cystic fibrosis, asthma, COPD, and bronchiolitis obliterans syndrome. This review summarizes the immunomodulatory properties of macrolides and the results of these recent studies demonstrating their potential for being disease-modifying agents.
Subject(s)
Immunomodulation/drug effects , Inflammation/drug therapy , Macrolides/therapeutic use , Respiratory Tract Diseases/drug therapy , Chronic Disease , Humans , Inflammation/immunology , Respiratory Tract Diseases/immunology , Time Factors , Treatment OutcomeABSTRACT
The current clinical classification of smoking-related lung disease fails to take into account the heterogeneity of chronic obstructive pulmonary disease (COPD). With an increased understanding of pathophysiologic variation, COPD now clearly represents a spectrum of overlapping diseases with important extrapulmonary consequences. A "phenotype" describes the outward physical manifestations of a particular disease, and compromises anything that is part of the observable structure, function or behavior of an individual. Such phenotypic distinctions in COPD include: frequent exacerbator, pulmonary cachectic, rapid decliner, airways hyperresponsiveness, impaired exercise tolerance, and emphysema versus airways disease. These variable manifestations, each with unique prognostic, clinical and physiologic ramifications, represent distinct phenotypes within COPD. While all of these phenotypes have smoking as a common risk factor, the other risk factors that determine these phenotypes remain poorly understood. An individual smoker has variable expression of each phenotype and there is mounting evidence that COPD phenotypes have different clinical outcomes. These phenotypes can be broadly classified into one of three groups: clinical, physiologic and radiographic. This review presents the evidence for the spectrum of COPD phenotypes with a focused discussion on the pathophysiologic, epidemiologic and clinical significance of each subtype.
