The study, led by Alexander Bertuccioli of the University of Urbino and colleagues across multiple Italian institutions, enrolled 120 participants diagnosed with vasomotor rhinitis, a condition now grouped under the broader umbrella of non-allergic rhinopathy. After accounting for withdrawals, 110 subjects completed the 20-day protocol: 58 received the lentisk oil nasal spray, a medical device marketed as Bactorinol, while 52 controls used isotonic saline alone. Participants were assigned through block randomization, and the trial was registered at ClinicalTrials.gov under identifier NCT07266688. Before enrollment, every candidate underwent skin prick testing and serum IgE measurement to rule out allergic sensitization, ensuring that the non-allergic classification was rigorous rather than assumed.

What makes this trial technically interesting is its dual evaluation strategy. The primary endpoints combined a patient-reported quality-of-life measure, the 22-item Sino-Nasal Outcome Test (SNOT-22), with an objective functional test: Peak Nasal Inspiratory Flow (PNIF), recorded with a calibrated mechanical flow meter during forced bilateral nasal inspiration. Three consecutive measurements were taken per session, and the highest value was used for analysis. Secondary endpoints went deeper still, into the microscopic world of the nasal mucosa. Using a Rhino-Probe sampler at the inferior turbinate, the researchers collected cytological specimens stained with May-Grünwald-Giemsa, then graded inflammatory cellularity—neutrophils, eosinophils, and mast cells—on a 0-to-4 semiquantitative scale, alongside bacterial abundance, the supranuclear stria, and cytological findings compatible with biofilm-like structures.

The statistical architecture relied on repeated-measures General Linear Models, with time as the within-subject factor and group and sex as between-subject factors, age as a covariate, and interaction terms probing whether treatment effects diverged over time. Pillai’s Trace served as the multivariate test statistic. Outliers were identified using the Tukey interquartile-range method and winsorized to boundary values, a conservative approach given the small number of extreme observations. The results were striking. SNOT-22 scores fell by 30.5 percent in the treatment group versus 9.7 percent in controls, a time-by-group interaction significant at p less than 0.001. The mean reduction of 12.73 points in treated patients exceeded the commonly cited minimal clinically important difference of roughly 9 points for SNOT-22, while the control group’s 3.35-point drop fell below that threshold.

Objective airflow told a parallel story. PNIF rose by 44.5 percent in treated subjects—from about 69.8 liters per minute at baseline to 100.9 liters per minute after 20 days—compared with a 20.8 percent gain in controls, with the between-group difference in change estimated at 16.32 liters per minute (95 percent confidence interval: 4.78 to 27.87; p = 0.006). Notably, the treatment group started with a heavier symptom burden: baseline SNOT-22 scores were significantly higher among treated patients (41.78 versus 34.72; p = 0.005), and cytological profiles revealed more neutrophils, mast cells, and eosinophils at the outset. Biofilm-like cytological findings were present in 50 percent of treated subjects versus 30.77 percent of controls before intervention. Despite this disadvantage, post-treatment outcomes favored the intervention group across the board.

The cytological results may prove the most provocative element. In the treated group, every subject with moderate or high bacterial abundance showed reduction over time; by day 20, no treated patient exhibited bacterial abundance above the mild level. The time-by-group interaction was significant for neutrophils (p = 0.001), mast cells (p = 0.021), bacterial abundance (p = 0.002), and biofilm-like structures (p = 0.001). Mast cells, the authors note, are increasingly recognized as effectors not only in allergic disease but also in neurogenic and non-IgE-mediated mucosal hyperreactivity, where crosstalk between neural pathways, epithelial barrier integrity, and innate immune activation may drive symptom generation. A reduction in these cellular markers alongside symptomatic improvement suggests the spray may exert a broader mucosal regulatory effect rather than a purely antimicrobial one.

The mechanistic rationale rests on the chemistry of the lentisk berry itself. Experimental work has shown that Pistacia lentiscus oil possesses antimicrobial activity against relevant upper airway pathogens, including Streptococcus species and Staphylococcus aureus, effects attributed to its unsaturated fatty acid fraction and bioactive anacardic acid derivatives. The oil used in the study was cold-pressed from ripe berries harvested during winter in southern Sardinia, then centrifuged and winterized—a fractionation process that removes fatty impurities and concentrates the lipophilic bioactive fractions implicated in anti-biofilm activity. Bacterial biofilms, highly organized microbial communities embedded in self-produced extracellular matrices, are notorious for resisting host defenses and conventional antimicrobials, and they have been extensively characterized in chronic rhinosinusitis. Whether they play an equivalent role in vasomotor rhinitis remains unproven, but the observed cytological trends are biologically coherent with that hypothesis.

The authors also frame their findings within an emerging ecological concept: that plant-derived bioactive compounds may act as modulators of host-associated microbial ecosystems rather than as blunt antimicrobial agents. This prebiotic-like perspective has been explored in gastrointestinal settings, where selected nutraceutical interventions influence inflammatory responses and microbial balance. Extending that framework to the upper airway mucosa opens translational avenues for chronic inflammatory conditions in which dysregulated host-microbe interactions may perpetuate symptoms—precisely the kind of mechanism that classical autonomic dysregulation models cannot fully explain.

Caveats abound, and the researchers are candid about them. Baseline heterogeneity between groups was substantial, particularly for SNOT-22 scores, sex distribution, and inflammatory cytology, and although statistical adjustment was applied, residual confounding cannot be excluded. Cytological assessment was performed in a non-blinded manner by a single trained investigator, so observer bias cannot be fully ruled out despite standardized sampling and staining. The intervention and control sprays were not fully placebo-matched, meaning differences in odor, viscosity, or sensory experience may have partially unblinded participants. The 20-day follow-up was short, limiting conclusions about durability, and cytology provides only indirect morphological evidence of bacterial presence rather than microbiological identification. One author, the study reports, serves as a scientific adviser to PharmExtracta, the device manufacturer, though the company had no role in study design, data analysis, or the decision to submit the manuscript.

These limitations temper but do not extinguish the study’s significance. Vasomotor rhinitis affects a large and heterogeneous population, degrading sleep quality, daytime performance, and overall well-being, yet current therapies—saline irrigation, intranasal corticosteroids, antihistamines, and in refractory cases surgical neurectomy—leave many patients undertreated. If a subset of non-allergic rhinopathy genuinely involves microbial persistence and biofilm-driven mucosal inflammation, then phytotherapeutic agents with microbial-modulating properties could carve out a genuinely new therapeutic niche. The authors call for larger randomized trials incorporating microbiological culture, molecular microbiome profiling, and longer follow-up to identify responder phenotypes and clarify mechanisms. Until then, the image of a Sardinian shrub’s winter berries easing the congested noses of modern patients stands as an exploratory but tantalizing data point in the evolving story of the nose as an ecosystem.

Subject of Research: A prospective controlled evaluation of winterized Pistacia lentiscus oil nasal spray in vasomotor rhinitis

Article Title: A prospective controlled evaluation of winterized Pistacia lentiscus oil nasal spray in vasomotor rhinitis

Article References: Bertuccioli, A., Belli, A., Sisti, D., Rocchi, M. B. L., Palazzi, C. M., Gelardi, M., La Mantia, I., Seccia, V., Masieri, S., Begvarfaj, E., Khan, A., & Macchi, A. (2026). A prospective controlled evaluation of winterized Pistacia lentiscus oil nasal spray in vasomotor rhinitis. Frontiers in Allergy, 7, Article 1946438. https://doi.org/10.3389/falgy.2026.1946438

Image Credits: AI Generated

DOI: 10.3389/falgy.2026.1946438

Keywords: prospective, controlled, evaluation, winterized, Pistacia, lentiscus, nasal, spray, vasomotor, rhinitis, scientific research