Resident Physician NYP Columbia Morgan Stanley Children's Hospital of New York Columbia University Irving Medical Center New York, New York, United States
Background: Respiratory complications are the leading causes of morbidity and mortality in sickle cell disease (SCD). The mechanisms of pulmonary disease in patients with SCD have not been completely characterized and underlying allergic and non-allergic inflammation may be involved.
Objective: The objective of our study was to characterize the inflammatory pathways involved in patients with pulmonary manifestations of SCD.
Design/Methods: We studied a cohort of 60 patients with SCD (age 3-18 years, 28 males) from a previously conducted 2-year clinical trial of monthly oral doses of vitamin D3 [high (100,000 IU/month) and low doses (12,000 IU/month)] to prevent respiratory complications, including respiratory infections, asthma exacerbations and acute chest syndrome (ACS). Both groups had reduced respiratory events at 2 years with no difference between groups. Inflammatory cytokines, including those associated with T-helper 1/T-helper 17 inflammation (IFN-γ, TNF, IL-2, IL-8, IL-17, IP-10), T-helper 2 inflammation (IL-4, IL-5, IL-9, IL-13), and monocyte activation (MCP-1, and IL-6) were assayed from stored serum samples by Luminex technology. Prospectively collected pulmonary function tests (PFT) and clinical information were abstracted by retrospective chart review. Statistical analysis was done on SAS software using Wilcoxon signed rank test, Spearman’s correlation tests, and multivariable linear regression analysis.
Results: At baseline, 45 patients (75%) had h/o ACS, 17 (28.3%) had h/o asthma, and 6 (10%) had allergic rhinitis. Forty two (72%) patients were on hydroxyurea. At baseline, 15 (26%) patients had an obstructive lung defect and 18 (43%) had a restrictive defect. Lung functions at 2 years were significantly lower for FEV1, FEV1/FVC, FEF25-75% and for TLC compared to baseline (Table). Spearman’s correlation analysis showed inverse correlations between IL-17A with TLC (r=-0.298, p=0.056) at baseline; and at 2 years, IL9 with FEV1 (r=-0.257, p=0.049) and FVC (r=-0.346, p=0.007) and IL-17A with FVC (r=-0.291, p=0.025). Patients with h/o ACS had borderline elevations of cytokine levels for TNFa (p=0.05), IL5 (p=0.082) and IP-10 (p=0.066). Multivariable linear modeling, adjusting for hydroxyurea showed asthma predicted FEV1 at baseline and at 2 years, FVC at baseline and 2 years while age, sex and history of ACS predicted TLC at baseline. Baseline PFT parameters predicted FEV1, FVC, FEV1/FVC, FEF25-75% and TLC at 2 years. Conclusion(s): Age, h/o asthma and ACS predicted PFTs parameters. Inflammatory cytokines may be playing a role in SCD related lung inflammation.
Pulmonary Function Tests at baseline and 2 years
Authors/Institutions: Sanford Williams, Columbia University Irving Medical Center, New York, New York, United States; Margaret T. Lee, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States; Yujing Yao, Columbia University Mailman School of Public Health, New York, New York, United States; Zhezhen Jin, Columbia University Mailman School of Public Health, New York, New York, United States; Gary M. Brittenham, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States; Meyer Kattan, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States; Aliva De, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States