Dr. E. Neil Schachter's laboratory offers a unique opportunity to study airway diseases on a number of different levels involving epidemiologic investigation, clinical challenge studies, and in vitro models of airway hypperreactivity. State-of-the-art technology for investigating environmental pollutants and occupational agents in an environmental chamber allow for applied investigation of the mechanisms by which pollutants cause airway disease and for studies of potential preventive measures can be instituted to safeguard against chronic lung disease. Pollutants studied include SO2, formaldehyde, environmen-tal tobacco smoke, NO2 and cotton bract. A unique model developed by this laboratory uses guinea tracheal rings in a series of organ baths to generate data to study receptor physiology. These investiga-tions allow a rapid approach to many of the questions raised by clinical and epidemio-logic data.

Despite recent advances, asthma continues to be a major, growing unconquered lung disease. Dr. Gwen Skloot has established a laboratory to introduce novel techniques in the study of airway hyperreactivity. She has demonstrated that lung volume "history" has a major impact on airway reactivity and that normals can be made "asthmatic" by restricting lung expansion. Recent work has shown that normal subjects can "protect" themselves from these symptoms of asthma by taking a single fast deep breath. The integration of this work with Dr. E. Neil Schachter's tracheal ring system has led to the development of a parallel in vitro model in which to study the response of the airway to stretch. Current studies using this model are focused on examining the effect of anti-inflammatory therapy on the response of the airway to stretch as well as the importance of the timing of initiation of anti-inflammatory therapy on the ability to modify this response. This in vitro model will be used to study the effect of anti-inflammatory therapy on both histology and pathophysiology. Ultimately, such a model could be important for screening anti-remodeling drugs developed for the treatment of asthma.

This is a nationwide network involving 19 centers that have joined forces to study important questions related to asthma. The network approach will facilitate multidisciplinary research by experts from a variety of research institutions that serve large populations of asthma patients. Dr. Gwen Skloot leads the investigative team at Mount Sinai. The first study evaluated the safety of the inactivated influenza vaccine in adults and children with asthma (N Engl J Med 2001;345:1529-36). This was a randomized, double-blind, placebo-controlled cross-over trial involving 2032 patients. The results demonstrated that there was no increase in the frequency of asthma exacerbations in patients who received the influenza vaccine vs. those who received placebo. The second study slated to begin this year will evaluate the effectiveness of low dose theophylline as add-on therapy for poorly controlled asthma. The study will compare low dose theophylline against a known, effective, once-a-day asthma treatment, montelukast, and against a placebo. A total of 627 patients with poorly controlled asthma will be treated for a period of six months. The main outcome measure will be the frequency of asthma flares that require the use of other medications or cause sudden worsening of lung function. If low dose theophylline proves to be effective in controlling asthma, it could have considerable impact on the treatment of the disease in terms of convenience and cost.

Studies by Drs. Marvin Lesser and Greg Schilero at the Bronx VA Hospital Quadriplegia Center have identified a heretofore undiscovered bronchial hyperreactivity in these patients. This work is being supported by the Disabled Veterans Association and has been the source of multiple studies and publications by fellows. The results of these studies promise to shed light on the mechanisms of asthma.