title: Macrolide therapy targets a specific phenotype in respiratory medicine: from clinical experience to basic science and back.
abstract: For centuries a quest has been going on for the "holy grail" in respiratory medicine: a treatment for numerous devastating chronic lung disorders. Yet, it is only a decade ago that pharmacological interference with the activation of the innate immune system by a macrolide antibiotic silently moved into everyday clinical practice. Macrolides, with their unique molecular structure built around a lactone ring, are now known to target harmful exaggerated innate immune responses. However, not all chronic lung conditions benefit from macrolide therapy and interestingly, neither do all patients with an apparently identical chronic lung disease. A subgroup of 'responders' seems to display a single specific phenotype that can be recognized in the various lung conditions and that seems to be related to inflammatory responses with a predominant innate immune system component. Recently we have contributed to the introduction of macrolide therapy in lung transplantation medicine. Also we attempted to analyse this phenotype by describing its clinical, immunological, histological and radiological characteristics. The aim of this manuscript is to review the use of macrolides in the respiratory field and to apply the macrolide-responsive phenotype beyond the setting of lung transplantation and other conditions in which macrolides have been successful. The description of this "universal" macrolide-responsive phenotype can both help rationalize macrolide therapy in respiratory disorders, in which its benefit is already well-known, as well as promote the use of this treatment in respiratory conditions of unknown etiology but with a "macrolide responsive phenotype".
authors.affiliation: Laboratory of Pneumology, Katholieke Universiteit Leuven, Herestraat 49, Leuven, Belgium.
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Robin
authors.initials: R
authors.lastname: Vos
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meyts
authors.forename: Stephanie I
authors.initials: SI
authors.lastname: De Vleeschauwer
authors.forename: Stijn E
authors.initials: SE
authors.lastname: Verleden
authors.forename: Anna
authors.initials: A
authors.lastname: Widyastuti-Willems
authors.forename: Wim A
authors.initials: WA
authors.lastname: Wuyts
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Van Raemdonck
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hoet
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Geert M
authors.initials: GM
authors.lastname: Verleden
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000473:pathology; D018942:Macrolides / Q000627:therapeutic use*; D010641:Phenotype; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000473:pathology; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018942:Macrolides; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human