[Frontiers in Bioscience 6, d973-985, August 1, 2001]


Anthony R. Mawson

College of Health Sciences, Des Moines University-Osteopathic Medical Center, 3200 Grand Avenue, Des Moines, Iowa 50312


1. Abstract
2. Introduction
3. Infection and Asthma-Clues to Etiology?
4. Retinoid Theory of Status Asthmaticus
5. Retinoids
6. Retinoid Intoxication and Asthma-Is there a Connection?
6.1. Vitamin A accumulates in the lung
6.2. Severe respiratory infections reduce vitamin A
6.3. Retinoic acid can be highly toxic
6.4. The manifestations of asthma resemble those of hypervitaminosis A
6.4.1. Retinoids enhance T-helper 2 cytokine production
6.4.2. Retinoic acid causes asthma-like effects
6.4.3. Retinoic acid causes mucus hypersecretion
6.4.4. Retinoic Acid, TGF-beta-1, and Airway Wall Remodeling
6.4.5. RA, Asthma, and Bone Marrow
6.5.Risk factors for asthma are associated with increased retinoid concentrations
6.5.1. Exercise
6.5.2. Diet
6.5.3. Nitric Oxide
6.6. Glucocorticoid treatment reduces retinoic acid
6.7. Remission in asthma in adolescence
6.8. Chemical-induced asthma
7. Conclusion
8. References


Asthma has become a major public health problem, affecting about 17 million people in the United States, including 4.8 million children. A striking increase in asthma and other forms of atopy has occurred in children in the U.S. and other western countries during the past 30 years. Several studies have reported an inverse association between childhood infectious illness and the development of atopy, suggesting that certain forms of infection protect against and even inhibit asthma. This may involve a shift in the balance of CD4 T lymphocyte helper cells from a Th2 to a Th1-type cytokine profile. However, the underlying mechanisms remain uncertain. Based on a review of the literature, it is conjectured that in the absence of certain types of childhood infection, retinoids (vitamin A and its congeners) accumulate in the lung. Later, upon exposure to known triggers for asthma, retinoid metabolites may be produced in such high concentration that they produce an acute, localized form of retinoid intoxication, recognized as status asthmaticus.