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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL097578-02
Application #
7918990
Study Section
Special Emphasis Panel (ZRG1-F10-S (21))
Program Officer
Rothgeb, Ann E
Project Start
2009-08-05
Project End
2011-08-04
Budget Start
2010-08-05
Budget End
2011-08-04
Support Year
2
Fiscal Year
2010
Total Cost
$59,918
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Campana, L M; Malhotra, A; Suki, B et al. (2013) The effect of lung stretch during sleep on airway mechanics in overweight and obese asthma. Respir Physiol Neurobiol 185:304-12
Owens, Robert L; Campana, Lisa M; Hess, Lauren et al. (2012) Sitting and supine esophageal pressures in overweight and obese subjects. Obesity (Silver Spring) 20:2354-60
Campana, Lisa M; Owens, R L; Suki, B et al. (2012) Measuring upper and lower airway resistance during sleep with the forced oscillation technique. Ann Biomed Eng 40:925-33
Owens, Robert L; Wellman, Andrew; Malhotra, Atul (2011) Which OSA Patients Might Respond to Nasal Valves? J Clin Sleep Med 7:23-4
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Owens, Robert L; Malhotra, Atul; Eckert, Danny J et al. (2010) The influence of end-expiratory lung volume on measurements of pharyngeal collapsibility. J Appl Physiol (1985) 108:445-51
Owens, Robert L; Malhotra, Atul (2010) Sleep-disordered breathing and COPD: the overlap syndrome. Respir Care 55:1333-44; discussion 1344-6
Owens, Robert L; Harris, R Scott; Malhotra, Atul (2009) Is the way to man's heart (and lung) through the abdomen? Crit Care 13:199