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

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
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Blaisdell, Carol J
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Washington University
Schools of Medicine
Saint Louis
United States
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Willen, Shaina M; Cohen, Robyn; Rodeghier, Mark et al. (2018) Age is a predictor of a small decrease in lung function in children with sickle cell anemia. Am J Hematol 93:408-415
Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C et al. (2018) Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia. Br J Haematol 180:571-577
Willen, Shaina M; Rodeghier, Mark; Rosen, Carol L et al. (2018) Sleep disordered breathing does not predict acute severe pain episodes in children with sickle cell anemia. Am J Hematol 93:478-485
Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C et al. (2017) Airway Hyperresponsiveness Does Not Predict Morbidity in Children with Sickle Cell Anemia. Am J Respir Crit Care Med 195:1533-1534
Cohen, Robyn T; Rodeghier, Mark; DeBaun, Michael R (2017) Reply: Decline of Lung Function in Children with Sickle Cell Disease Is Not Associated with Restrictive Defects. Ann Am Thorac Soc 14:478
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
McClain, Brandi L; Ivy, Zalaya K; Bryant, Valencia et al. (2016) Improved Guideline Adherence With Integrated Sickle Cell Disease and Asthma Care. Am J Prev Med 51:S62-8
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
Karafin, Matthew S; Dogra, Shibani; Rodeghier, Mark et al. (2016) Increased circulating fibrocytes are associated with higher reticulocyte percent in children with sickle cell anemia. Pediatr Pulmonol 51:295-9

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