The Role of Lung Volumes in Asthma

Brigham And Women'S Hospital, Boston MA

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Abstract

DESCRIPTION (provided by applicant): Asthma is a chronic respiratory disease characterized by ainway inflammation and airway hyper- responsiveness, which causes airflow obstruction. It is extremely prevalent, affecting an estimated 7.7% (22 million) of all Americans, and costly with loss of productivity and direct healthcare costs in the billions of dollars. The incidence and prevalence of asthma are increasing, both in the US and around the world. This increase comes despite greater understanding of the inflammatory and allergic basis for asthma, and despite better anti-inflammatory medications. One explanation for the increasing prevalence of asthma is the concomitant increase in obesity, with the majority of Americans now overweight or obese. Numerous studies have linked asthma and obesity, and demonstrated increased obstruction with weight gain and decreased obstruction with weight loss. However, the mechanisms that underlie this linkage are not known. We believe that low lung volumes contribute to the pathogenesis and severity of asthma. Lung volumes are decreased in obesity, and likely fall further during sleep, particularly in overweight and obese patients. Both upper and lower airway resistance increase with decreasing lung volumes, as airways become smaller. However, prior work showed that lower airway resistance increases out of proportion to the decrease in lung volume that occurs during sleep in asthma patients. This difference between controls and patients with asthma has not been further explored, yet may provide insight into asthma pathogenesis and provide potential targets for therapy. Therefore, we purpose a series of experiments to define the impact of lung volumes during sleep on airway resistance. Technology already in use in our lab will be applied to patients with asthma and controls. Nocturnal airway resistance will be measured continuously using the forced oscillation technique (FOT), a non-invasive measurement that is ideal for use during sleep. Lung volumes can be monitored with magnetometers, and esophageal manometry will be used to measure transpulmonary pressures. Furthermore, we will manipulate lung volumes during sleep both tonically (using negative extra-thoracic pressure) and dynamically (using bi-level positive airway pressure). Asthma is an extremely common disorder, which is becoming more prevalent. The purpose of this study is to examine how nocturnal lung volumes contribute to asthma severity, which may explain part of the link between asthma and obesity. Our work may lead to new targets for therapy.