Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance and hyperreactivity) is an intrinsic component of SCD and may contribute to excess SCD morbidity and mortality. Inhaled corticosteroids (ICS), a safe and effective therapy for pulmonary inflammation in asthma, may ameliorate the altered pulmonary physiologic milieu in SCD. With this single-center, longitudinal, randomized, triple-blind, placebo controlled trial we studied the efficacy and feasibility of ICS in 54 non-asthmatic individuals with SCD. Participants received once daily mometasone furoate 220 mcg dry powder inhalation or placebo for 16 weeks. The primary outcome was feasibility (the number who complete the trial divided by the total number enrolled) with pre-specified efficacy outcomes including daily pain score over time (patient reported) and change in soluble vascular cell adhesion molecule (sVCAM) levels between entry and 8-weeks. For the primary outcome of feasibility, the result was 96% (52 of 54, 95% CI 87% – 99%) for the intent-to-treat analysis and 83% (45 of 54, 95% CI 71% – 91%) for the per-protocol analysis. The adjusted treatment effect of mometasone was a reduction in daily pain score of 1.42 points (95%CI 0.61 – 2.21, p = 0.001). Mometasone was associated with a reduction in sVCAM levels of 526.94 ng/mL more than placebo (95% CI 50.66 – 1,003.23, p = 0.03). These results support further study of ICS in SCD including multi-center trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202)

Background Adults with sickle cell disease (SCD) have an increased prevalence of pulmonary hypertension (PAH), associated with significant morbidity and mortality. This finding has not been validated in children. We carried out a prospective comparison of echocardiography (echo) data between SCD and control patients and a correlation between echo findings and hematologic and pulmonary function testing (PFT) in SCD patients. Methods Children with SCD and age and gender matched controls were prospectively enrolled during well visits. Each subject underwent a history and examination, echo, hematologic testing, and PFT. Echo data was compared between SCD patients and controls, and regression analysis was performed to assess for correlation between echo parameters and anemia, markers of hemolysis, and PFT in SCD patients. Results Of the 194 SCD patients and 29 controls enrolled, 180 SCD patients and 26 controls had measurable tricuspid valve regurgitation (TR) to estimate systolic pulmonary pressure. TR, left ventricle (LV) size and LV mass were significantly higher in children with SCD (Table 1 ). Linear regression analysis in SCD patients showed that TR, LV size, LV mass, and diastolic function (E/E TDI ) correlated significantly with hemoglobin, markers of hemolysis, and obstructive pulmonary disease (Table 2 ). There was no correlation between echo parameters and age, blood pressure, or measures of restrictive lung disease Conclusion Children with SCD have higher estimated pulmonary pressure, LV size and mass and a trend toward worse diastolic function when compared to controls. TR and LV size and mass correlate with anemia, hemolysis, and obstructive patterns on PFT. Table 1 - Comparative Data Table 2 - Regression Analysis

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