A 48-week clinical trial of adults with sickle cell disease and episodic respiratory symptoms found that daily use of inhaled mometasone increased soluble VCAM-1, a marker of disease severity, by 40% compared to placebo. Researchers recommend confirming an asthma diagnosis before prescribing inhaled corticosteroids to these patients.
Adults living with sickle cell disease frequently experience episodic coughing and wheezing even without an established asthma diagnosis. Clinicians sometimes prescribe inhaled corticosteroids off-label to manage these symptoms based on short-term data. A new phase 2 clinical trial investigated the long-term safety of this approach over nearly a year of continuous treatment.
Mometasone Raises VCAM-1 Levels Without Changing Pain or ER Visits
- Biomarker Impact: Daily use of the inhaled steroid mometasone raised levels of soluble vascular cell adhesion molecule 1 (VCAM-1), a marker of disease severity.
- Diagnostic Caution: The study authors advise clinicians to strictly confirm an asthma diagnosis before initiating inhaled corticosteroids in patients with sickle cell disease.
- Clinical Endpoint: While biological markers shifted upward, the trial did not find statistically significant differences in daily pain ratings or emergency room visits between the treatment and placebo groups.
Phase 2 Trial Methodology and Findings
Susanna A. Curtis, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York City led the single-center study. Researchers enrolled 77 adults who experienced episodic cough and wheeze within the prior two months. Participants were randomized to receive either once-daily mometasone or a placebo inhaler for 48 weeks, with follow-up concluding at week 52.
The primary outcome measured the percentage change in soluble VCAM-1 from baseline to the end of the study. Soluble VCAM-1 increased by 42% in the mometasone group relative to the placebo arm. Furthermore, intercellular adhesion molecule 3 (ICAM-3) also rose significantly more among patients using the steroid.
| Outcome Measure | Mometasone Group | Placebo Group | Statistical Significance |
|---|---|---|---|
| Soluble VCAM-1 Change | +42% increase | Reference | P = .02 |
| ICAM-3 Elevation | +0.23% rise | Reference | P = .02 |
| Acute Chest Syndrome Episodes | 8 episodes (5 patients) | 4 episodes (3 patients) | Not significant |
| Serious Adverse Events | 15 events | 11 events | — |
Laboratory Markers and Adverse Events Showed No Significant Differences
Other laboratory markers, including standard tests for hemolysis and organ damage, did not differ significantly between the two cohorts. Rates of emergency department visits, acute pain visits, intensive care unit admissions, and acute chest syndrome trended higher with mometasone, but these differences lacked statistical significance.
Serious adverse events totaled 26 across the trial, with 15 occurring in the mometasone group and 11 in the placebo group. The events in the steroid group included one new asthma diagnosis and one stroke, while no deaths were recorded during the 52-week observation window. Non-serious side effects like sore throat and oral thrush showed no significant variance.
“As there is a high prevalence of isolated asthma-like characteristics in individuals with SCD, such as airway hyperactivity and wheezing, it is critical to confirm a diagnosis of asthma in a person with SCD before starting inhaled corticosteroids,” the study authors wrote, as published in JAMA Network Open.
Avoid Inhaled Corticosteroids Without Confirmed Asthma Diagnosis
Patients with sickle cell disease who experience isolated coughing or wheezing without a confirmed, concurrent asthma diagnosis should avoid starting inhaled corticosteroids without thorough pulmonary evaluation. Because these medications may elevate vascular adhesion markers and disease severity indicators, off-label use requires strict clinical justification.
Individuals currently prescribed inhaled steroids who experience worsening pain crises, acute chest symptoms, or neurological changes must contact their hematologist or primary care physician immediately. Do not discontinue prescribed respiratory medications abruptly without professional medical supervision.
Evaluating Future Research Trajectories
The National Institutes of Health funded the single-center investigation, which provided data on pulmonary interventions in non-asthmatic sickle cell cohorts. However, the small sample size and single-center design limit the broader generalizability of these findings. Future investigations must determine whether these biomarker shifts translate into long-term organ damage or if pediatric populations and patients with concurrent asthma respond differently.
References
- Curtis, S. A., et al. JAMA Network Open, published online.
Always seek the advice of a qualified physician regarding any medical condition.
