New insights into the pathogenesis of asthma

Historical perspectiveAsthma is a disease whose ability to cause episodic symptomatology has been appreciated since antiquity.Although the fine points of the definition can be debated, it is reasonable to think of asthma as a pulmonary disorder characterized by the generalized reversible obstruction of airflow and to define reversibility as a greater than 12% increase in the patient's forced expiratory volume in 1 second (FEV 1 ) that occurs either spontaneously or with therapy.Airway hyperresponsiveness, an exaggerated bronchospastic response to nonspecific agents such as methacholine and histamine or specific antigens, is the physiologic cornerstone of this disorder.A diagnosis of asthma is established based on a history of recurrent wheeze, cough, or shortness of breath, reversible airway obstruction demonstrated by pulmonary-function testing, and, in cases where questions exist, a methacholine challenge demonstrating airway hyperresponsiveness.It has long been assumed that patients with asthma experience intermittent attacks and have relatively normal lung function during intervening periods.More recent studies have demonstrated that asthma can cause progressive lung impairment and, in some patients, eventuate in partially reversible or irreversible airway obstruction.Any discussion of asthma must take into account the recent increase in its prevalence.Since approximately 1980, the frequency of this disorder has almost doubled.As a result of this "epidemic," asthma now affects approximately 8-10% of the population in the US, is the leading cause of hospitalization among children less than 15 years of age, and costs society billions of dollars annually.This increase in prevalence is not simply due to diagnostic transference or increased diagnostic awareness, since asthma mortality rates have also increased during this interval.