Intranasal Corticosteroid Efficacy Affirmed in Pediatric Chronic Rhinosinusitis

Intranasal corticosteroids (INCs) improved quality of life for children suffering from chronic rhinosinusitis, the RAISE randomized trial showed.

Sinus and Nasal Quality of Life Survey (SN-5) scores improved significantly more for children assigned to daily intranasal mometasone spray (Nasonex) along with daily saline solution rinsing with a nasal nebulizer compared with the saline routine alone, reported Piotr Łacwik, MD, PhD, of Jan Kochanowski University in Kielce, Poland, and coauthors in JAMA Pediatrics.

SN-5 scores fell from 3.6 to 3.1 after 12 weeks of INC use, whereas the scores of children in the saline control group rose from 3.4 to 3.8 over the same period, an average between-group difference of -0.58 points (95% CI -1.31 to -0.19).

While perhaps not surprising, the finding can be considered “novel and important” due to the lack of randomized INC trials in kids, the researchers wrote.

In previous studies, the difference between moderate and mild chronic rhinosinusitis was 0.8 points on the 7-point scale, for which higher scores indicate more severe sinonasal symptoms.

“Further work is needed to investigate the long-term efficacy and safety of INCs, but we believe that our observations significantly reinforce the recommendation of INCs as a first-line treatment of CRS [chronic rhinosinusitis] in children,” Łacwik’s group concluded.

Their trial included 63 children ages 4 to 8 years old (average 6 years, 60% male) randomized to open-label treatment to either intranasal mometasone via an atomizer for a total of 12 weeks (one application in each nostril daily) along with daily nasal nebulizer treatment with 3 mL of a sodium chloride 0.9% solution, or to the nasal nebulizer alone.

Enrollment required at least two chronic rhinosinusitis symptoms, including cough, nasal blockage, obstruction, pressure, facial pain, nasal discharge or congestion, for a minimum of 12 weeks prior to the study.

A clinically significant shift in SN-5 score of 0.5 points or greater was more than three times more likely among the INC-treated patients (OR 3.33, 95% CI 1.08-10.3).

Among the secondary outcomes, INC treatment was linked to a significant change in nasopharyngeal microbiome richness (OR 1.09, 95% CI 1.01-1.19), with an increase in operational taxonomic units richness within the nasopharynx microbiome. This increase in diversity was also directly associated with significant clinical improvement (OR 4.6, 95% CI 1.1-19.9) after adjustment for the effect of the INC, “implying a possible causative relationship,” according to Łacwik and colleagues.

INC-treated patients also saw a greater reduction of nasal innate lymphoid cell-3 abundance in comparison to their control counterparts.

“Although the cause of chronic rhinosinusitis is not fully understood, a growing body of research suggests that the breakdown of the sinonasal microbiome may play a significant role in its development and as such could be a potential target for future treatment strategies,” the group wrote. “Similarly, innate lymphoid cells (ILCs) are reported to be actively involved in several inflammatory diseases, but their specific contributions to the cause of CRS remain to be fully understood.”

INC treatment appeared to be effective across demographic characteristics represented within the participant population, as no significant differences were observed between male and female patients or by whether or not the patient had allergies. The authors suggested that the improvement of the sinonasal microbiome accounted for this positive result.

“It may be hypothesized that the corticosteroid-related shifts of the microbiome could be driven by several factors associated with the anti-inflammatory action of topical corticosteroids, including alleviation of inflammation and edema, reduction in residual nasal discharge, and promoting commensal bacterial growth,” they wrote. “Moreover, a reduced immunological response could possibly allow for further diversification of species present in the sinonasal cavity.”

Limitations to the study included its open-label design and relatively small sample size, warranting further study on a larger population.

“While INCs are widely considered safe for long-term use, subsequent long-term observations would be helpful to further confirm their prolonged efficacy and safety in children,” the group wrote.