title: Inhaled steroids reduce pain and sVCAM levels in individuals with sickle cell disease: A triple-blind, randomized trial.
abstract: Clinical and preclinical data demonstrate that altered pulmonary physiology (including increased inflammation, increased blood flow, airway resistance, and hyper-reactivity) is an intrinsic component of Sickle Cell Disease (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 nonasthmatic 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 prespecified 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 50.66-1003.23, P = 0.03). These results support further study of ICS in SCD including multicenter trials and longer durations of treatment. www.clinicaltrials.gov (NCT02061202).
authors.affiliation: Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Glassberg
authors.affiliation: Department of Oncology, Montefiore Medical Center, Bronx, New York.
authors.forename: Caterina
authors.initials: C
authors.lastname: Minnitti
authors.affiliation: Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai Beth Israel, New York.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cromwell
authors.affiliation: Department of Hematology and Oncology, Icahn School of Medicine at Mount Sinai Beth Israel, New York.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Cytryn
authors.affiliation: Center for Therapeutic Antibody Development, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraus
authors.affiliation: Department of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Gwen S
authors.initials: GS
authors.lastname: Skloot
authors.affiliation: Berry Consultants, Austin, Texas.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Connor
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Adeeb H
authors.initials: AH
authors.lastname: Rahman
authors.affiliation: Departments of Emergency Medicine and Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: William J
authors.initials: WJ
authors.lastname: Meurer
mesh_terms: D056586:Acute Chest Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D000280:Administration, Inhalation; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D000986:Antisickling Agents / Q000627:therapeutic use; D015415:Biomarkers; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D016017:Odds Ratio; D010146:Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D012129:Respiratory Function Tests; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D000986:Antisickling Agents; D015415:Biomarkers; D016207:Cytokines; D013256:Steroids; D019010:Vascular Cell Adhesion Molecule-1