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Key Words atopy, cytokines, Th-2 cells, airway obstruction, bronchial hyperreactivity, lungs
* Abstract Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyperreactivity, and airway remodeling. The etiology of asthma is complex and multifactorial. Recent advances have demonstrated the importance of genetics in the development of asthma, particularly atopic asthma. Environmental stimuli, particularly early childhood infections, have also been associated with the development of asthma. Most current data seem to suggest that these factors drive the development of a Th-2 lymphocyte-predominant immune response, which has been associated with atopy and IgE-mediated inflammation. The concept of reversible airflow obstruction has also recently been challenged. It is now clear that chronic airway changes occur, which may contribute to progressive airflow obstruction. We discuss the important influence of genetic and environmental factors on the emergence of the asthmatic phenotype. The significance of Th-1 and Th-2 lymphocyte-mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.
INTRODUCTION
Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyperreactivity (AHR), and airway remodeling (1). An estimated 15 million Americans are affected by asthma and the morbidity and mortality associated with it is increasing in industrialized nations (2, 3). Morbidity is disproportionately high among inner-city residents (4). The annual cost of caring for asthmatics exceeds six billion dollars per year in the United States, and the worldwide market for asthma medication is currently valued at 5.5 billion dollars each year (5).
ETIOLOGY
The etiology of asthma is complex and multifactorial. It involves the interaction between genetic factors and environmental stimuli. The vast majority of the data regarding the pathogenesis of asthma concentrates on atopic asthma and the imbalance between the Th-1 (cell-mediated immunity) and Th-2 (humorally mediated immunity) phenotypes. However, asthma (reversible airflow obstruction, persistent AHR, and airway remodeling) may also occur through nonallergic mechanisms of inflammation. Genetics, the uterine environment, maternal and infant diet, respiratory infections, and occupational and environmental exposures all contribute to this delicate balance. The manner in which all these factors converge will determine whether the reaction of a particular subject's immune system results in airway inflammation and airway...