This is a renewal application to continue our work on the Sleep and Asthma Cohort (SAC) Study, HL079937, in which we started enrolling subjects in May 2006. Our overall goal is to elucidate the effects that asthma risk factors and sleep disordered breathing (SDB) have on sickle cell disease (SCD) morbidity and to better understand the biological basis progression of lung disease. In the SAC Study, we established a unique cohort of 251 children with SCD, who have received both pulmonary function testing (PFT) and full polysomnography (PSG), the largest cohort of children with SCD with this extensive evaluation in the world. Currently, the cohort has a mean prospective follow- up period of only 2.1 years, a time insufficient to assess the relationship between asthma risk factors on SCD-related morbidity (hospitalization for pain or ACS). At present, we do not know the relationship between asthma risk factors, SDB, and lung function abnormalities. We propose following the existing cohort for additional 4 years to assess these relationships with adequate statistical power. Further, our translational research efforts have focused on establishing a pre-clinical transgenic SCD mouse model of lung disease that strongly implicates fibrocytes, as a key component to pulmonary fibrosis and abnormal lung function. The project will have three inter-related Aims: 1) To determine if asthma risk factors (parental history of asthma and positive skin test for an aeroallergen) are associated with an increase incidence of pain and ACS episodes.
Aim 2, to determine relationship between SDB and the presence of, or progression to, obstructive lung disease.
Aim 3, to determine the longitudinal relationship between the percentage and phenotypes of circulating fibrocytes and evolution of abnormal lung function. Together, the results of this highly interactive collaboration of clinical and basic scientists will permit new insights into the natural history and pathogenesis of lung and sleep disease in SCD, providing a strong foundation for future targeted therapy.

Public Health Relevance

Pulmonary complications are a leading cause of morbidity and mortality in sickle cell disease;yet, the natural history, risk factors and underlying mechanisms of progressive lung disease are poorly defined. The overall goal of this applications is to identify the laboratory and clinical determinants of how lung disease progresses from normal in early childhood to asthma and later to a severe lung disease that requires oxygen

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL079937-08
Application #
8528686
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Blaisdell, Carol J
Project Start
2005-08-25
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
8
Fiscal Year
2013
Total Cost
$622,472
Indirect Cost
$76,419
Name
Vanderbilt University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Cohen, Robyn T; Rodeghier, Mark; Kirkham, Fenella J et al. (2016) Exhaled nitric oxide: Not associated with asthma, symptoms, or spirometry in children with sickle cell anemia. J Allergy Clin Immunol 138:1338-1343.e4
DeBaun, Michael R; Strunk, Robert C (2016) The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia. Lancet 387:2545-53
Cohen, Robyn T; Strunk, Robert C; Rodeghier, Mark et al. (2016) Pattern of Lung Function Is Not Associated with Prior or Future Morbidity in Children with Sickle Cell Anemia. Ann Am Thorac Soc 13:1314-23
Kassim, Adetola A; Payne, Amanda B; Rodeghier, Mark et al. (2015) Low forced expiratory volume is associated with earlier death in sickle cell anemia. Blood 126:1544-50
Galadanci, Najibah A; Liang, Wayne H; Galadanci, Aisha A et al. (2015) Wheezing is common in children with sickle cell disease when compared with controls. J Pediatr Hematol Oncol 37:16-9
Andreotti, Charissa; King, Allison A; Macy, Elizabeth et al. (2015) The Association of Cytokine Levels With Cognitive Function in Children With Sickle Cell Disease and Normal MRI Studies of the Brain. J Child Neurol 30:1349-53
Vance, Leah D; Rodeghier, Mark; Cohen, Robyn T et al. (2015) Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and asthma cohort. Am J Hematol 90:371-5
Strunk, Robert C; Cohen, Robyn T; Cooper, Benjamin P et al. (2014) Wheezing symptoms and parental asthma are associated with a physician diagnosis of asthma in children with sickle cell anemia. J Pediatr 164:821-826.e1
DeBaun, Michael R; Rodeghier, Mark; Cohen, Robyn et al. (2014) Factors predicting future ACS episodes in children with sickle cell anemia. Am J Hematol 89:E212-7
Glassberg, Jeffrey A; Strunk, Robert; DeBaun, Michael R (2014) Wheezing in children with sickle cell disease. Curr Opin Pediatr 26:9-18

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