Novel mechanistic targets for the treatment of sub-acute and chronic bronchitis.
Sub-acute and chronic bronchitis (SACB) are among the least well studied major medical problems that exist today. While much research and novel drug discovery have focused on asthma, comparatively little has been performed on chronic bronchitis, the fourth or fifth most frequent disease (4 to 6% of the population over 45 years of age), or on sub-acute bronchitis, the persistent symptoms of a respiratory infection which is the major reason Americans visit a physician (20%). This lack of attention is largely due to difficulties associated with modeling the pathophysiology of SACB in vitro, in situ, in organs or in animals as well as the presumption that drugs developed for asthma would also be effective in SACB. Data with bronchodilators (anti-cholinergics versus beta2-adrenergic agonist) and corticosteroids have strongly dismissed that premise. In this review of potential novel mechanistic targets directed specifically at SACB, an emphasis is given to recent data, gathered most convincingly from tissues and patients with cystic fibrosis, that have led to an appreciation of the critical role respiratory epithelial dysfunction plays in the pathophysiology and symptoms of these diseases. Mechanistic targets that restore (normalize or accelerate) airway 'cleansing' (enhance host defense) by accelerating mucociliary clearance are described and given preference over anti-inflammatory mechanisms that could further impair host defense.
Wegner
C D
CD
Pharmacia Discovery Research, 4901 Searle Parkway (Room J-322A), Skokie, Illinois 60077, USA. craig.d.wegner@monsanto.com
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use; D001991:Bronchitis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers
D000305:Adrenal Cortex Hormones; D000975:Antioxidants; D001993:Bronchodilator Agents; C546385:P2RY2 protein, human; D058910:Purinergic P2 Receptor Agonists; D058473:Receptors, Purinergic P2Y2; D026941:Sodium Channel Blockers